The Toll-Like Receptor 4 (TLR4) Variant rs2149356 and Risk of Gout in European and Polynesian Sample Sets
Identifieur interne : 003051 ( Ncbi/Merge ); précédent : 003050; suivant : 003052The Toll-Like Receptor 4 (TLR4) Variant rs2149356 and Risk of Gout in European and Polynesian Sample Sets
Auteurs : Humaira Rasheed [Nouvelle-Zélande, Pakistan] ; Cushla Mckinney [Nouvelle-Zélande] ; Lisa K. Stamp [Nouvelle-Zélande] ; Nicola Dalbeth [Nouvelle-Zélande] ; Ruth K. Topless [Nouvelle-Zélande] ; Richard Day [Australie] ; Diluk Kannangara [Australie] ; Kenneth Williams [Australie] ; Malcolm Smith [Australie] ; Matthijs Janssen [Pays-Bas] ; Tim L. Jansen [Pays-Bas] ; Leo A. Joosten [Pays-Bas] ; Timothy R. Radstake [Pays-Bas] ; Philip L. Riches [Royaume-Uni] ; Anne-Kathrin Tausche [Allemagne] ; Frederic Lioté [France] ; Leo Lu [États-Unis] ; Eli A. Stahl [États-Unis] ; Hyon K. Choi [États-Unis] ; Alexander So [Suisse] ; Tony R. Merriman [Nouvelle-Zélande]Source :
- PLoS ONE [ 1932-6203 ] ; 2016.
Descripteurs français
- KwdFr :
- MESH :
English descriptors
- KwdEn :
- MESH :
- chemical , genetics : Toll-Like Receptor 4.
- genetics : European Continental Ancestry Group, Gout, Oceanic Ancestry Group.
- Adult, Female, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Risk Factors.
Abstract
Deposition of crystallized monosodium urate (MSU) in joints as a result of hyperuricemia is a central risk factor for gout. However other factors must exist that control the progression from hyperuricaemia to gout. A previous genetic association study has implicated the toll-like receptor 4 (TLR4) which activates the NLRP3 inflammasome via the nuclear factor-κB signaling pathway upon stimulation by MSU crystals. The T-allele of single nucleotide polymorphism
Url:
DOI: 10.1371/journal.pone.0147939
PubMed: 26808548
PubMed Central: 4726773
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PMC:4726773Le document en format XML
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<affiliation wicri:level="3"><nlm:aff id="aff006"><addr-line>Department of Clinical Pharmacology & Toxicology, St Vincent’s Hospital, Sydney, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Clinical Pharmacology & Toxicology, St Vincent’s Hospital, Sydney</wicri:regionArea>
<placeName><settlement type="city">Sydney</settlement>
<region type="état">Nouvelle-Galles du Sud</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Williams, Kenneth" sort="Williams, Kenneth" uniqKey="Williams K" first="Kenneth" last="Williams">Kenneth Williams</name>
<affiliation wicri:level="3"><nlm:aff id="aff005"><addr-line>School of Medical Sciences, University of New South Wales, Sydney, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>School of Medical Sciences, University of New South Wales, Sydney</wicri:regionArea>
<placeName><settlement type="city">Sydney</settlement>
<region type="état">Nouvelle-Galles du Sud</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="aff006"><addr-line>Department of Clinical Pharmacology & Toxicology, St Vincent’s Hospital, Sydney, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Clinical Pharmacology & Toxicology, St Vincent’s Hospital, Sydney</wicri:regionArea>
<placeName><settlement type="city">Sydney</settlement>
<region type="état">Nouvelle-Galles du Sud</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Smith, Malcolm" sort="Smith, Malcolm" uniqKey="Smith M" first="Malcolm" last="Smith">Malcolm Smith</name>
<affiliation wicri:level="1"><nlm:aff id="aff007"><addr-line>Department of Medicine, Flinders Medical Centre and Repatriation General Hospital, Adelaide, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Medicine, Flinders Medical Centre and Repatriation General Hospital, Adelaide</wicri:regionArea>
<wicri:noRegion>Adelaide</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Janssen, Matthijs" sort="Janssen, Matthijs" uniqKey="Janssen M" first="Matthijs" last="Janssen">Matthijs Janssen</name>
<affiliation wicri:level="1"><nlm:aff id="aff008"><addr-line>Department of Rheumatology, Rijnstate Hospital, Arnhem, The Netherlands</addr-line>
</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Rheumatology, Rijnstate Hospital, Arnhem</wicri:regionArea>
<wicri:noRegion>Arnhem</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Jansen, Tim L" sort="Jansen, Tim L" uniqKey="Jansen T" first="Tim L." last="Jansen">Tim L. Jansen</name>
<affiliation wicri:level="1"><nlm:aff id="aff009"><addr-line>Department of IQ HealthCare, VieCuri Medical Centre, Venlo, The Netherlands</addr-line>
</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of IQ HealthCare, VieCuri Medical Centre, Venlo</wicri:regionArea>
<wicri:noRegion>Venlo</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Joosten, Leo A" sort="Joosten, Leo A" uniqKey="Joosten L" first="Leo A." last="Joosten">Leo A. Joosten</name>
<affiliation wicri:level="3"><nlm:aff id="aff010"><addr-line>Department of Internal Medicine and Radboud Institute of Molecular Life Science, Radboud University Medical Center, Nijmegen, The Netherlands</addr-line>
</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Internal Medicine and Radboud Institute of Molecular Life Science, Radboud University Medical Center, Nijmegen</wicri:regionArea>
<placeName><settlement type="city">Nimègue</settlement>
<region type="province" nuts="2">Gueldre</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Radstake, Timothy R" sort="Radstake, Timothy R" uniqKey="Radstake T" first="Timothy R." last="Radstake">Timothy R. Radstake</name>
<affiliation wicri:level="3"><nlm:aff id="aff011"><addr-line>Department of Rheumatology and Clinical Immunology, Laboratory of Translational Immunology, Department of Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands</addr-line>
</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Rheumatology and Clinical Immunology, Laboratory of Translational Immunology, Department of Immunology, University Medical Centre Utrecht, Utrecht</wicri:regionArea>
<placeName><settlement type="city">Utrecht</settlement>
<region nuts="2" type="province">Utrecht (province)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Riches, Philip L" sort="Riches, Philip L" uniqKey="Riches P" first="Philip L." last="Riches">Philip L. Riches</name>
<affiliation wicri:level="4"><nlm:aff id="aff012"><addr-line>Rheumatic Diseases Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom</addr-line>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Rheumatic Diseases Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh</wicri:regionArea>
<placeName><settlement type="city">Édimbourg</settlement>
<region type="country">Écosse</region>
<settlement type="city">Édimbourg</settlement>
</placeName>
<orgName type="university">Université d'Édimbourg</orgName>
</affiliation>
</author>
<author><name sortKey="Tausche, Anne Kathrin" sort="Tausche, Anne Kathrin" uniqKey="Tausche A" first="Anne-Kathrin" last="Tausche">Anne-Kathrin Tausche</name>
<affiliation wicri:level="3"><nlm:aff id="aff013"><addr-line>Department of Rheumatology, University Clinic “Carl-Gustav-Carus”, Dresden, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Rheumatology, University Clinic “Carl-Gustav-Carus”, Dresden</wicri:regionArea>
<placeName><region type="land" nuts="1">Saxe (Land)</region>
<region type="district" nuts="2">District de Dresde</region>
<settlement type="city">Dresde</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Liote, Frederic" sort="Liote, Frederic" uniqKey="Liote F" first="Frederic" last="Lioté">Frederic Lioté</name>
<affiliation wicri:level="3"><nlm:aff id="aff014"><addr-line>INSERM, UMR-S 1132, Hospital Lariboisière, Paris, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM, UMR-S 1132, Hospital Lariboisière, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="aff015"><addr-line>University Paris Diderot (UFR de Médecine), Sorbonne Paris Cité, Paris, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>University Paris Diderot (UFR de Médecine), Sorbonne Paris Cité, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Lu, Leo" sort="Lu, Leo" uniqKey="Lu L" first="Leo" last="Lu">Leo Lu</name>
<affiliation wicri:level="2"><nlm:aff id="aff016"><addr-line>Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Stahl, Eli A" sort="Stahl, Eli A" uniqKey="Stahl E" first="Eli A." last="Stahl">Eli A. Stahl</name>
<affiliation wicri:level="2"><nlm:aff id="aff017"><addr-line>Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY</wicri:regionArea>
<placeName><region type="state">État de New York</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Choi, Hyon K" sort="Choi, Hyon K" uniqKey="Choi H" first="Hyon K." last="Choi">Hyon K. Choi</name>
<affiliation wicri:level="2"><nlm:aff id="aff016"><addr-line>Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="So, Alexander" sort="So, Alexander" uniqKey="So A" first="Alexander" last="So">Alexander So</name>
<affiliation wicri:level="3"><nlm:aff id="aff018"><addr-line>DAL, Service of Rheumatology, Laboratory of Rheumatology, University of Lausanne, CHUV, Nestlé, Lausanne, Switzerland</addr-line>
</nlm:aff>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>DAL, Service of Rheumatology, Laboratory of Rheumatology, University of Lausanne, CHUV, Nestlé, Lausanne</wicri:regionArea>
<placeName><settlement type="city">Lausanne</settlement>
<region nuts="3" type="region">Canton de Vaud</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Merriman, Tony R" sort="Merriman, Tony R" uniqKey="Merriman T" first="Tony R." last="Merriman">Tony R. Merriman</name>
<affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Department of Biochemistry, University of Otago, Dunedin, New Zealand</addr-line>
</nlm:aff>
<country xml:lang="fr">Nouvelle-Zélande</country>
<wicri:regionArea>Department of Biochemistry, University of Otago, Dunedin</wicri:regionArea>
<wicri:noRegion>Dunedin</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">PLoS ONE</title>
<idno type="eISSN">1932-6203</idno>
<imprint><date when="2016">2016</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term>
<term>European Continental Ancestry Group (genetics)</term>
<term>Female</term>
<term>Genetic Predisposition to Disease</term>
<term>Gout (genetics)</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Oceanic Ancestry Group (genetics)</term>
<term>Risk Factors</term>
<term>Toll-Like Receptor 4 (genetics)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Facteurs de risque</term>
<term>Femelle</term>
<term>Goutte (génétique)</term>
<term>Humains</term>
<term>Mâle</term>
<term>Population d'origine européenne (génétique)</term>
<term>Population d'origine océanique (génétique)</term>
<term>Prédisposition génétique à une maladie</term>
<term>Récepteur de type Toll-4 (génétique)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Toll-Like Receptor 4</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>European Continental Ancestry Group</term>
<term>Gout</term>
<term>Oceanic Ancestry Group</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Goutte</term>
<term>Population d'origine européenne</term>
<term>Population d'origine océanique</term>
<term>Récepteur de type Toll-4</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Adult</term>
<term>Female</term>
<term>Genetic Predisposition to Disease</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Risk Factors</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Facteurs de risque</term>
<term>Femelle</term>
<term>Humains</term>
<term>Mâle</term>
<term>Prédisposition génétique à une maladie</term>
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<front><div type="abstract" xml:lang="en"><p>Deposition of crystallized monosodium urate (MSU) in joints as a result of hyperuricemia is a central risk factor for gout. However other factors must exist that control the progression from hyperuricaemia to gout. A previous genetic association study has implicated the toll-like receptor 4 (TLR4) which activates the NLRP3 inflammasome via the nuclear factor-κB signaling pathway upon stimulation by MSU crystals. The T-allele of single nucleotide polymorphism <italic>rs2149356</italic>
in <italic>TLR4</italic>
is a risk factor associated with gout in a Chinese study. Our aim was to replicate this observation in participants of European and New Zealand Polynesian (Māori and Pacific) ancestry. A total of 2250 clinically-ascertained prevalent gout cases and 13925 controls were used. Non-clinically-ascertained incident gout cases and controls from the Health Professional Follow-up (HPFS) and Nurses Health Studies (NHS) were also used. Genotypes were derived from genome-wide genotype data or directly obtained using Taqman. Logistic regression analysis was done including age, sex, diuretic exposure and ancestry as covariates as appropriate. The T-allele increased the risk of gout in the clinically-ascertained European samples (OR = 1.12, <italic>P</italic>
= 0.012) and decreased the risk of gout in Polynesians (OR = 0.80, <italic>P</italic>
= 0.011). There was no evidence for association in the HPFS or NHS sample sets. In conclusion <italic>TLR4</italic>
SNP <italic>rs2143956</italic>
associates with gout risk in prevalent clinically-ascertained gout in Europeans, in a direction consistent with previously published results in Han Chinese. However, with an opposite direction of association in Polynesians and no evidence for association in a non-clinically-ascertained incident gout cohort this variant should be analysed in other international gout genetic data sets to determine if there is genuine evidence for association.</p>
</div>
</front>
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<double pmid="26808548"><pmc><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">The Toll-Like Receptor 4 (TLR4) Variant <italic>rs2149356</italic>
and Risk of Gout in European and Polynesian Sample Sets</title>
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<country xml:lang="fr">Pakistan</country>
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</author>
<author><name sortKey="Mckinney, Cushla" sort="Mckinney, Cushla" uniqKey="Mckinney C" first="Cushla" last="Mckinney">Cushla Mckinney</name>
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</nlm:aff>
<country xml:lang="fr">Nouvelle-Zélande</country>
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</affiliation>
</author>
<author><name sortKey="Stamp, Lisa K" sort="Stamp, Lisa K" uniqKey="Stamp L" first="Lisa K." last="Stamp">Lisa K. Stamp</name>
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</nlm:aff>
<country xml:lang="fr">Nouvelle-Zélande</country>
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</affiliation>
</author>
<author><name sortKey="Dalbeth, Nicola" sort="Dalbeth, Nicola" uniqKey="Dalbeth N" first="Nicola" last="Dalbeth">Nicola Dalbeth</name>
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<country xml:lang="fr">Nouvelle-Zélande</country>
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</author>
<author><name sortKey="Topless, Ruth K" sort="Topless, Ruth K" uniqKey="Topless R" first="Ruth K." last="Topless">Ruth K. Topless</name>
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</nlm:aff>
<country xml:lang="fr">Nouvelle-Zélande</country>
<wicri:regionArea>Department of Biochemistry, University of Otago, Dunedin</wicri:regionArea>
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</affiliation>
</author>
<author><name sortKey="Day, Richard" sort="Day, Richard" uniqKey="Day R" first="Richard" last="Day">Richard Day</name>
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<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Clinical Pharmacology & Toxicology, St Vincent’s Hospital, Sydney</wicri:regionArea>
<placeName><settlement type="city">Sydney</settlement>
<region type="état">Nouvelle-Galles du Sud</region>
</placeName>
</affiliation>
</author>
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</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Clinical Pharmacology & Toxicology, St Vincent’s Hospital, Sydney</wicri:regionArea>
<placeName><settlement type="city">Sydney</settlement>
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</placeName>
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</nlm:aff>
<country xml:lang="fr">Australie</country>
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</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Clinical Pharmacology & Toxicology, St Vincent’s Hospital, Sydney</wicri:regionArea>
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</placeName>
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</nlm:aff>
<country xml:lang="fr">Australie</country>
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<author><name sortKey="Janssen, Matthijs" sort="Janssen, Matthijs" uniqKey="Janssen M" first="Matthijs" last="Janssen">Matthijs Janssen</name>
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<country xml:lang="fr">Pays-Bas</country>
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</affiliation>
</author>
<author><name sortKey="Jansen, Tim L" sort="Jansen, Tim L" uniqKey="Jansen T" first="Tim L." last="Jansen">Tim L. Jansen</name>
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</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of IQ HealthCare, VieCuri Medical Centre, Venlo</wicri:regionArea>
<wicri:noRegion>Venlo</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Joosten, Leo A" sort="Joosten, Leo A" uniqKey="Joosten L" first="Leo A." last="Joosten">Leo A. Joosten</name>
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</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Internal Medicine and Radboud Institute of Molecular Life Science, Radboud University Medical Center, Nijmegen</wicri:regionArea>
<placeName><settlement type="city">Nimègue</settlement>
<region type="province" nuts="2">Gueldre</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Radstake, Timothy R" sort="Radstake, Timothy R" uniqKey="Radstake T" first="Timothy R." last="Radstake">Timothy R. Radstake</name>
<affiliation wicri:level="3"><nlm:aff id="aff011"><addr-line>Department of Rheumatology and Clinical Immunology, Laboratory of Translational Immunology, Department of Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands</addr-line>
</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Rheumatology and Clinical Immunology, Laboratory of Translational Immunology, Department of Immunology, University Medical Centre Utrecht, Utrecht</wicri:regionArea>
<placeName><settlement type="city">Utrecht</settlement>
<region nuts="2" type="province">Utrecht (province)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Riches, Philip L" sort="Riches, Philip L" uniqKey="Riches P" first="Philip L." last="Riches">Philip L. Riches</name>
<affiliation wicri:level="4"><nlm:aff id="aff012"><addr-line>Rheumatic Diseases Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom</addr-line>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Rheumatic Diseases Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh</wicri:regionArea>
<placeName><settlement type="city">Édimbourg</settlement>
<region type="country">Écosse</region>
<settlement type="city">Édimbourg</settlement>
</placeName>
<orgName type="university">Université d'Édimbourg</orgName>
</affiliation>
</author>
<author><name sortKey="Tausche, Anne Kathrin" sort="Tausche, Anne Kathrin" uniqKey="Tausche A" first="Anne-Kathrin" last="Tausche">Anne-Kathrin Tausche</name>
<affiliation wicri:level="3"><nlm:aff id="aff013"><addr-line>Department of Rheumatology, University Clinic “Carl-Gustav-Carus”, Dresden, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Rheumatology, University Clinic “Carl-Gustav-Carus”, Dresden</wicri:regionArea>
<placeName><region type="land" nuts="1">Saxe (Land)</region>
<region type="district" nuts="2">District de Dresde</region>
<settlement type="city">Dresde</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Liote, Frederic" sort="Liote, Frederic" uniqKey="Liote F" first="Frederic" last="Lioté">Frederic Lioté</name>
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</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM, UMR-S 1132, Hospital Lariboisière, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="aff015"><addr-line>University Paris Diderot (UFR de Médecine), Sorbonne Paris Cité, Paris, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>University Paris Diderot (UFR de Médecine), Sorbonne Paris Cité, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Lu, Leo" sort="Lu, Leo" uniqKey="Lu L" first="Leo" last="Lu">Leo Lu</name>
<affiliation wicri:level="2"><nlm:aff id="aff016"><addr-line>Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Stahl, Eli A" sort="Stahl, Eli A" uniqKey="Stahl E" first="Eli A." last="Stahl">Eli A. Stahl</name>
<affiliation wicri:level="2"><nlm:aff id="aff017"><addr-line>Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY</wicri:regionArea>
<placeName><region type="state">État de New York</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Choi, Hyon K" sort="Choi, Hyon K" uniqKey="Choi H" first="Hyon K." last="Choi">Hyon K. Choi</name>
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</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA</wicri:regionArea>
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</placeName>
</affiliation>
</author>
<author><name sortKey="So, Alexander" sort="So, Alexander" uniqKey="So A" first="Alexander" last="So">Alexander So</name>
<affiliation wicri:level="3"><nlm:aff id="aff018"><addr-line>DAL, Service of Rheumatology, Laboratory of Rheumatology, University of Lausanne, CHUV, Nestlé, Lausanne, Switzerland</addr-line>
</nlm:aff>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>DAL, Service of Rheumatology, Laboratory of Rheumatology, University of Lausanne, CHUV, Nestlé, Lausanne</wicri:regionArea>
<placeName><settlement type="city">Lausanne</settlement>
<region nuts="3" type="region">Canton de Vaud</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Merriman, Tony R" sort="Merriman, Tony R" uniqKey="Merriman T" first="Tony R." last="Merriman">Tony R. Merriman</name>
<affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Department of Biochemistry, University of Otago, Dunedin, New Zealand</addr-line>
</nlm:aff>
<country xml:lang="fr">Nouvelle-Zélande</country>
<wicri:regionArea>Department of Biochemistry, University of Otago, Dunedin</wicri:regionArea>
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</affiliation>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">The Toll-Like Receptor 4 (TLR4) Variant <italic>rs2149356</italic>
and Risk of Gout in European and Polynesian Sample Sets</title>
<author><name sortKey="Rasheed, Humaira" sort="Rasheed, Humaira" uniqKey="Rasheed H" first="Humaira" last="Rasheed">Humaira Rasheed</name>
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</nlm:aff>
<country xml:lang="fr">Nouvelle-Zélande</country>
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<wicri:noRegion>Dunedin</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff002"><addr-line>University of Engineering and Technology, Lahore, Pakistan</addr-line>
</nlm:aff>
<country xml:lang="fr">Pakistan</country>
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</affiliation>
</author>
<author><name sortKey="Mckinney, Cushla" sort="Mckinney, Cushla" uniqKey="Mckinney C" first="Cushla" last="Mckinney">Cushla Mckinney</name>
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</nlm:aff>
<country xml:lang="fr">Nouvelle-Zélande</country>
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<wicri:noRegion>Dunedin</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Stamp, Lisa K" sort="Stamp, Lisa K" uniqKey="Stamp L" first="Lisa K." last="Stamp">Lisa K. Stamp</name>
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</nlm:aff>
<country xml:lang="fr">Nouvelle-Zélande</country>
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</affiliation>
</author>
<author><name sortKey="Dalbeth, Nicola" sort="Dalbeth, Nicola" uniqKey="Dalbeth N" first="Nicola" last="Dalbeth">Nicola Dalbeth</name>
<affiliation wicri:level="1"><nlm:aff id="aff004"><addr-line>Department of Medicine, University of Auckland, Auckland, New Zealand</addr-line>
</nlm:aff>
<country xml:lang="fr">Nouvelle-Zélande</country>
<wicri:regionArea>Department of Medicine, University of Auckland, Auckland</wicri:regionArea>
<wicri:noRegion>Auckland</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Topless, Ruth K" sort="Topless, Ruth K" uniqKey="Topless R" first="Ruth K." last="Topless">Ruth K. Topless</name>
<affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Department of Biochemistry, University of Otago, Dunedin, New Zealand</addr-line>
</nlm:aff>
<country xml:lang="fr">Nouvelle-Zélande</country>
<wicri:regionArea>Department of Biochemistry, University of Otago, Dunedin</wicri:regionArea>
<wicri:noRegion>Dunedin</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Day, Richard" sort="Day, Richard" uniqKey="Day R" first="Richard" last="Day">Richard Day</name>
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</nlm:aff>
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<placeName><settlement type="city">Sydney</settlement>
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</placeName>
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</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Clinical Pharmacology & Toxicology, St Vincent’s Hospital, Sydney</wicri:regionArea>
<placeName><settlement type="city">Sydney</settlement>
<region type="état">Nouvelle-Galles du Sud</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Kannangara, Diluk" sort="Kannangara, Diluk" uniqKey="Kannangara D" first="Diluk" last="Kannangara">Diluk Kannangara</name>
<affiliation wicri:level="3"><nlm:aff id="aff005"><addr-line>School of Medical Sciences, University of New South Wales, Sydney, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>School of Medical Sciences, University of New South Wales, Sydney</wicri:regionArea>
<placeName><settlement type="city">Sydney</settlement>
<region type="état">Nouvelle-Galles du Sud</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="aff006"><addr-line>Department of Clinical Pharmacology & Toxicology, St Vincent’s Hospital, Sydney, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Clinical Pharmacology & Toxicology, St Vincent’s Hospital, Sydney</wicri:regionArea>
<placeName><settlement type="city">Sydney</settlement>
<region type="état">Nouvelle-Galles du Sud</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Williams, Kenneth" sort="Williams, Kenneth" uniqKey="Williams K" first="Kenneth" last="Williams">Kenneth Williams</name>
<affiliation wicri:level="3"><nlm:aff id="aff005"><addr-line>School of Medical Sciences, University of New South Wales, Sydney, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>School of Medical Sciences, University of New South Wales, Sydney</wicri:regionArea>
<placeName><settlement type="city">Sydney</settlement>
<region type="état">Nouvelle-Galles du Sud</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="aff006"><addr-line>Department of Clinical Pharmacology & Toxicology, St Vincent’s Hospital, Sydney, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Clinical Pharmacology & Toxicology, St Vincent’s Hospital, Sydney</wicri:regionArea>
<placeName><settlement type="city">Sydney</settlement>
<region type="état">Nouvelle-Galles du Sud</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Smith, Malcolm" sort="Smith, Malcolm" uniqKey="Smith M" first="Malcolm" last="Smith">Malcolm Smith</name>
<affiliation wicri:level="1"><nlm:aff id="aff007"><addr-line>Department of Medicine, Flinders Medical Centre and Repatriation General Hospital, Adelaide, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Medicine, Flinders Medical Centre and Repatriation General Hospital, Adelaide</wicri:regionArea>
<wicri:noRegion>Adelaide</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Janssen, Matthijs" sort="Janssen, Matthijs" uniqKey="Janssen M" first="Matthijs" last="Janssen">Matthijs Janssen</name>
<affiliation wicri:level="1"><nlm:aff id="aff008"><addr-line>Department of Rheumatology, Rijnstate Hospital, Arnhem, The Netherlands</addr-line>
</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Rheumatology, Rijnstate Hospital, Arnhem</wicri:regionArea>
<wicri:noRegion>Arnhem</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Jansen, Tim L" sort="Jansen, Tim L" uniqKey="Jansen T" first="Tim L." last="Jansen">Tim L. Jansen</name>
<affiliation wicri:level="1"><nlm:aff id="aff009"><addr-line>Department of IQ HealthCare, VieCuri Medical Centre, Venlo, The Netherlands</addr-line>
</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of IQ HealthCare, VieCuri Medical Centre, Venlo</wicri:regionArea>
<wicri:noRegion>Venlo</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Joosten, Leo A" sort="Joosten, Leo A" uniqKey="Joosten L" first="Leo A." last="Joosten">Leo A. Joosten</name>
<affiliation wicri:level="3"><nlm:aff id="aff010"><addr-line>Department of Internal Medicine and Radboud Institute of Molecular Life Science, Radboud University Medical Center, Nijmegen, The Netherlands</addr-line>
</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Internal Medicine and Radboud Institute of Molecular Life Science, Radboud University Medical Center, Nijmegen</wicri:regionArea>
<placeName><settlement type="city">Nimègue</settlement>
<region type="province" nuts="2">Gueldre</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Radstake, Timothy R" sort="Radstake, Timothy R" uniqKey="Radstake T" first="Timothy R." last="Radstake">Timothy R. Radstake</name>
<affiliation wicri:level="3"><nlm:aff id="aff011"><addr-line>Department of Rheumatology and Clinical Immunology, Laboratory of Translational Immunology, Department of Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands</addr-line>
</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Rheumatology and Clinical Immunology, Laboratory of Translational Immunology, Department of Immunology, University Medical Centre Utrecht, Utrecht</wicri:regionArea>
<placeName><settlement type="city">Utrecht</settlement>
<region nuts="2" type="province">Utrecht (province)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Riches, Philip L" sort="Riches, Philip L" uniqKey="Riches P" first="Philip L." last="Riches">Philip L. Riches</name>
<affiliation wicri:level="4"><nlm:aff id="aff012"><addr-line>Rheumatic Diseases Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom</addr-line>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Rheumatic Diseases Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh</wicri:regionArea>
<placeName><settlement type="city">Édimbourg</settlement>
<region type="country">Écosse</region>
<settlement type="city">Édimbourg</settlement>
</placeName>
<orgName type="university">Université d'Édimbourg</orgName>
</affiliation>
</author>
<author><name sortKey="Tausche, Anne Kathrin" sort="Tausche, Anne Kathrin" uniqKey="Tausche A" first="Anne-Kathrin" last="Tausche">Anne-Kathrin Tausche</name>
<affiliation wicri:level="3"><nlm:aff id="aff013"><addr-line>Department of Rheumatology, University Clinic “Carl-Gustav-Carus”, Dresden, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Rheumatology, University Clinic “Carl-Gustav-Carus”, Dresden</wicri:regionArea>
<placeName><region type="land" nuts="1">Saxe (Land)</region>
<region type="district" nuts="2">District de Dresde</region>
<settlement type="city">Dresde</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Liote, Frederic" sort="Liote, Frederic" uniqKey="Liote F" first="Frederic" last="Lioté">Frederic Lioté</name>
<affiliation wicri:level="3"><nlm:aff id="aff014"><addr-line>INSERM, UMR-S 1132, Hospital Lariboisière, Paris, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM, UMR-S 1132, Hospital Lariboisière, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="aff015"><addr-line>University Paris Diderot (UFR de Médecine), Sorbonne Paris Cité, Paris, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>University Paris Diderot (UFR de Médecine), Sorbonne Paris Cité, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Lu, Leo" sort="Lu, Leo" uniqKey="Lu L" first="Leo" last="Lu">Leo Lu</name>
<affiliation wicri:level="2"><nlm:aff id="aff016"><addr-line>Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Stahl, Eli A" sort="Stahl, Eli A" uniqKey="Stahl E" first="Eli A." last="Stahl">Eli A. Stahl</name>
<affiliation wicri:level="2"><nlm:aff id="aff017"><addr-line>Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY</wicri:regionArea>
<placeName><region type="state">État de New York</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Choi, Hyon K" sort="Choi, Hyon K" uniqKey="Choi H" first="Hyon K." last="Choi">Hyon K. Choi</name>
<affiliation wicri:level="2"><nlm:aff id="aff016"><addr-line>Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="So, Alexander" sort="So, Alexander" uniqKey="So A" first="Alexander" last="So">Alexander So</name>
<affiliation wicri:level="3"><nlm:aff id="aff018"><addr-line>DAL, Service of Rheumatology, Laboratory of Rheumatology, University of Lausanne, CHUV, Nestlé, Lausanne, Switzerland</addr-line>
</nlm:aff>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>DAL, Service of Rheumatology, Laboratory of Rheumatology, University of Lausanne, CHUV, Nestlé, Lausanne</wicri:regionArea>
<placeName><settlement type="city">Lausanne</settlement>
<region nuts="3" type="region">Canton de Vaud</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Merriman, Tony R" sort="Merriman, Tony R" uniqKey="Merriman T" first="Tony R." last="Merriman">Tony R. Merriman</name>
<affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Department of Biochemistry, University of Otago, Dunedin, New Zealand</addr-line>
</nlm:aff>
<country xml:lang="fr">Nouvelle-Zélande</country>
<wicri:regionArea>Department of Biochemistry, University of Otago, Dunedin</wicri:regionArea>
<wicri:noRegion>Dunedin</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">PLoS ONE</title>
<idno type="eISSN">1932-6203</idno>
<imprint><date when="2016">2016</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
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<front><div type="abstract" xml:lang="en"><p>Deposition of crystallized monosodium urate (MSU) in joints as a result of hyperuricemia is a central risk factor for gout. However other factors must exist that control the progression from hyperuricaemia to gout. A previous genetic association study has implicated the toll-like receptor 4 (TLR4) which activates the NLRP3 inflammasome via the nuclear factor-κB signaling pathway upon stimulation by MSU crystals. The T-allele of single nucleotide polymorphism <italic>rs2149356</italic>
in <italic>TLR4</italic>
is a risk factor associated with gout in a Chinese study. Our aim was to replicate this observation in participants of European and New Zealand Polynesian (Māori and Pacific) ancestry. A total of 2250 clinically-ascertained prevalent gout cases and 13925 controls were used. Non-clinically-ascertained incident gout cases and controls from the Health Professional Follow-up (HPFS) and Nurses Health Studies (NHS) were also used. Genotypes were derived from genome-wide genotype data or directly obtained using Taqman. Logistic regression analysis was done including age, sex, diuretic exposure and ancestry as covariates as appropriate. The T-allele increased the risk of gout in the clinically-ascertained European samples (OR = 1.12, <italic>P</italic>
= 0.012) and decreased the risk of gout in Polynesians (OR = 0.80, <italic>P</italic>
= 0.011). There was no evidence for association in the HPFS or NHS sample sets. In conclusion <italic>TLR4</italic>
SNP <italic>rs2143956</italic>
associates with gout risk in prevalent clinically-ascertained gout in Europeans, in a direction consistent with previously published results in Han Chinese. However, with an opposite direction of association in Polynesians and no evidence for association in a non-clinically-ascertained incident gout cohort this variant should be analysed in other international gout genetic data sets to determine if there is genuine evidence for association.</p>
</div>
</front>
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<author><name sortKey="Hanssen, S" uniqKey="Hanssen S">S Hanssen</name>
</author>
<author><name sortKey="Netea, Mg" uniqKey="Netea M">MG Netea</name>
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</author>
<author><name sortKey="Barrera, P" uniqKey="Barrera P">P Barrera</name>
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<pubmed><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">The Toll-Like Receptor 4 (TLR4) Variant rs2149356 and Risk of Gout in European and Polynesian Sample Sets.</title>
<author><name sortKey="Rasheed, Humaira" sort="Rasheed, Humaira" uniqKey="Rasheed H" first="Humaira" last="Rasheed">Humaira Rasheed</name>
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</affiliation>
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</affiliation>
</author>
<author><name sortKey="Stamp, Lisa K" sort="Stamp, Lisa K" uniqKey="Stamp L" first="Lisa K" last="Stamp">Lisa K. Stamp</name>
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</affiliation>
</author>
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</affiliation>
</author>
<author><name sortKey="Topless, Ruth K" sort="Topless, Ruth K" uniqKey="Topless R" first="Ruth K" last="Topless">Ruth K. Topless</name>
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</affiliation>
</author>
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</placeName>
</affiliation>
</author>
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</affiliation>
</author>
<author><name sortKey="Joosten, Leo A" sort="Joosten, Leo A" uniqKey="Joosten L" first="Leo A" last="Joosten">Leo A. Joosten</name>
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</placeName>
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<author><name sortKey="Liote, Frederic" sort="Liote, Frederic" uniqKey="Liote F" first="Frederic" last="Lioté">Frederic Lioté</name>
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</placeName>
</affiliation>
</author>
<author><name sortKey="Lu, Leo" sort="Lu, Leo" uniqKey="Lu L" first="Leo" last="Lu">Leo Lu</name>
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<author><name sortKey="Stahl, Eli A" sort="Stahl, Eli A" uniqKey="Stahl E" first="Eli A" last="Stahl">Eli A. Stahl</name>
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<author><name sortKey="Choi, Hyon K" sort="Choi, Hyon K" uniqKey="Choi H" first="Hyon K" last="Choi">Hyon K. Choi</name>
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<author><name sortKey="So, Alexander" sort="So, Alexander" uniqKey="So A" first="Alexander" last="So">Alexander So</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">The Toll-Like Receptor 4 (TLR4) Variant rs2149356 and Risk of Gout in European and Polynesian Sample Sets.</title>
<author><name sortKey="Rasheed, Humaira" sort="Rasheed, Humaira" uniqKey="Rasheed H" first="Humaira" last="Rasheed">Humaira Rasheed</name>
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</affiliation>
</author>
<author><name sortKey="Mckinney, Cushla" sort="Mckinney, Cushla" uniqKey="Mckinney C" first="Cushla" last="Mckinney">Cushla Mckinney</name>
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</affiliation>
</author>
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</affiliation>
</author>
<author><name sortKey="Dalbeth, Nicola" sort="Dalbeth, Nicola" uniqKey="Dalbeth N" first="Nicola" last="Dalbeth">Nicola Dalbeth</name>
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</affiliation>
</author>
<author><name sortKey="Topless, Ruth K" sort="Topless, Ruth K" uniqKey="Topless R" first="Ruth K" last="Topless">Ruth K. Topless</name>
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</affiliation>
</author>
<author><name sortKey="Day, Richard" sort="Day, Richard" uniqKey="Day R" first="Richard" last="Day">Richard Day</name>
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</placeName>
</affiliation>
</author>
<author><name sortKey="Kannangara, Diluk" sort="Kannangara, Diluk" uniqKey="Kannangara D" first="Diluk" last="Kannangara">Diluk Kannangara</name>
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</placeName>
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</placeName>
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<author><name sortKey="Smith, Malcolm" sort="Smith, Malcolm" uniqKey="Smith M" first="Malcolm" last="Smith">Malcolm Smith</name>
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</affiliation>
</author>
<author><name sortKey="Janssen, Matthijs" sort="Janssen, Matthijs" uniqKey="Janssen M" first="Matthijs" last="Janssen">Matthijs Janssen</name>
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<country xml:lang="fr">Pays-Bas</country>
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<wicri:noRegion>Arnhem</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Jansen, Tim L" sort="Jansen, Tim L" uniqKey="Jansen T" first="Tim L" last="Jansen">Tim L. Jansen</name>
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<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of IQ HealthCare, VieCuri Medical Centre, Venlo</wicri:regionArea>
<wicri:noRegion>Venlo</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Joosten, Leo A" sort="Joosten, Leo A" uniqKey="Joosten L" first="Leo A" last="Joosten">Leo A. Joosten</name>
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<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Internal Medicine and Radboud Institute of Molecular Life Science, Radboud University Medical Center, Nijmegen</wicri:regionArea>
<placeName><settlement type="city">Nimègue</settlement>
<region type="province" nuts="2">Gueldre</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Radstake, Timothy R" sort="Radstake, Timothy R" uniqKey="Radstake T" first="Timothy R" last="Radstake">Timothy R. Radstake</name>
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<country xml:lang="fr">Pays-Bas</country>
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<placeName><settlement type="city">Utrecht</settlement>
<region nuts="2" type="province">Utrecht (province)</region>
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<author><name sortKey="Riches, Philip L" sort="Riches, Philip L" uniqKey="Riches P" first="Philip L" last="Riches">Philip L. Riches</name>
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<placeName><settlement type="city">Édimbourg</settlement>
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<settlement type="city">Édimbourg</settlement>
</placeName>
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<author><name sortKey="Tausche, Anne Kathrin" sort="Tausche, Anne Kathrin" uniqKey="Tausche A" first="Anne-Kathrin" last="Tausche">Anne-Kathrin Tausche</name>
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<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Rheumatology, University Clinic "Carl-Gustav-Carus", Dresden</wicri:regionArea>
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<region type="district" nuts="2">District de Dresde</region>
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</author>
<author><name sortKey="Liote, Frederic" sort="Liote, Frederic" uniqKey="Liote F" first="Frederic" last="Lioté">Frederic Lioté</name>
<affiliation wicri:level="3"><nlm:affiliation>INSERM, UMR-S 1132, Hospital Lariboisière, Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM, UMR-S 1132, Hospital Lariboisière, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Lu, Leo" sort="Lu, Leo" uniqKey="Lu L" first="Leo" last="Lu">Leo Lu</name>
<affiliation wicri:level="2"><nlm:affiliation>Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Stahl, Eli A" sort="Stahl, Eli A" uniqKey="Stahl E" first="Eli A" last="Stahl">Eli A. Stahl</name>
<affiliation wicri:level="2"><nlm:affiliation>Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY</wicri:regionArea>
<placeName><region type="state">État de New York</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Choi, Hyon K" sort="Choi, Hyon K" uniqKey="Choi H" first="Hyon K" last="Choi">Hyon K. Choi</name>
<affiliation wicri:level="2"><nlm:affiliation>Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="So, Alexander" sort="So, Alexander" uniqKey="So A" first="Alexander" last="So">Alexander So</name>
<affiliation wicri:level="3"><nlm:affiliation>DAL, Service of Rheumatology, Laboratory of Rheumatology, University of Lausanne, CHUV, Nestlé, Lausanne, Switzerland.</nlm:affiliation>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>DAL, Service of Rheumatology, Laboratory of Rheumatology, University of Lausanne, CHUV, Nestlé, Lausanne</wicri:regionArea>
<placeName><settlement type="city">Lausanne</settlement>
<region nuts="3" type="region">Canton de Vaud</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Merriman, Tony R" sort="Merriman, Tony R" uniqKey="Merriman T" first="Tony R" last="Merriman">Tony R. Merriman</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry, University of Otago, Dunedin, New Zealand.</nlm:affiliation>
<country xml:lang="fr">Nouvelle-Zélande</country>
<wicri:regionArea>Department of Biochemistry, University of Otago, Dunedin</wicri:regionArea>
<wicri:noRegion>Dunedin</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">PloS one</title>
<idno type="eISSN">1932-6203</idno>
<imprint><date when="2016" type="published">2016</date>
</imprint>
</series>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term>
<term>European Continental Ancestry Group (genetics)</term>
<term>Female</term>
<term>Genetic Predisposition to Disease</term>
<term>Gout (genetics)</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Oceanic Ancestry Group (genetics)</term>
<term>Risk Factors</term>
<term>Toll-Like Receptor 4 (genetics)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Facteurs de risque</term>
<term>Femelle</term>
<term>Goutte (génétique)</term>
<term>Humains</term>
<term>Mâle</term>
<term>Population d'origine européenne (génétique)</term>
<term>Population d'origine océanique (génétique)</term>
<term>Prédisposition génétique à une maladie</term>
<term>Récepteur de type Toll-4 (génétique)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Toll-Like Receptor 4</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>European Continental Ancestry Group</term>
<term>Gout</term>
<term>Oceanic Ancestry Group</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Goutte</term>
<term>Population d'origine européenne</term>
<term>Population d'origine océanique</term>
<term>Récepteur de type Toll-4</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Adult</term>
<term>Female</term>
<term>Genetic Predisposition to Disease</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Risk Factors</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Facteurs de risque</term>
<term>Femelle</term>
<term>Humains</term>
<term>Mâle</term>
<term>Prédisposition génétique à une maladie</term>
</keywords>
</textClass>
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<front><div type="abstract" xml:lang="en">Deposition of crystallized monosodium urate (MSU) in joints as a result of hyperuricemia is a central risk factor for gout. However other factors must exist that control the progression from hyperuricaemia to gout. A previous genetic association study has implicated the toll-like receptor 4 (TLR4) which activates the NLRP3 inflammasome via the nuclear factor-κB signaling pathway upon stimulation by MSU crystals. The T-allele of single nucleotide polymorphism rs2149356 in TLR4 is a risk factor associated with gout in a Chinese study. Our aim was to replicate this observation in participants of European and New Zealand Polynesian (Māori and Pacific) ancestry. A total of 2250 clinically-ascertained prevalent gout cases and 13925 controls were used. Non-clinically-ascertained incident gout cases and controls from the Health Professional Follow-up (HPFS) and Nurses Health Studies (NHS) were also used. Genotypes were derived from genome-wide genotype data or directly obtained using Taqman. Logistic regression analysis was done including age, sex, diuretic exposure and ancestry as covariates as appropriate. The T-allele increased the risk of gout in the clinically-ascertained European samples (OR = 1.12, P = 0.012) and decreased the risk of gout in Polynesians (OR = 0.80, P = 0.011). There was no evidence for association in the HPFS or NHS sample sets. In conclusion TLR4 SNP rs2143956 associates with gout risk in prevalent clinically-ascertained gout in Europeans, in a direction consistent with previously published results in Han Chinese. However, with an opposite direction of association in Polynesians and no evidence for association in a non-clinically-ascertained incident gout cohort this variant should be analysed in other international gout genetic data sets to determine if there is genuine evidence for association.</div>
</front>
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