GWAS identifies an NAT2 acetylator status tag single nucleotide polymorphism to be a major locus for skin fluorescence
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Auteurs : Karen M. Eny ; Helen L. Lutgers [Pays-Bas] ; John Maynard [États-Unis] ; Barbara E. K. Klein [États-Unis] ; Kristine E. Lee [États-Unis] ; Gil Atzmon [États-Unis] ; Vincent M. Monnier [États-Unis] ; Jana V. Van Vliet-Ostaptchouk [Pays-Bas] ; Reindert Graaff [Pays-Bas] ; Pim Van Der Harst [Pays-Bas] ; Harold Snieder [Pays-Bas] ; Melanie M. Van Der Klauw [Pays-Bas] ; David R. Sell [États-Unis] ; S. Mohsen Hosseini ; Patricia A. Cleary [États-Unis] ; Barbara H. Braffett [États-Unis] ; Trevor J. Orchard [États-Unis] ; Timothy J. Lyons [Royaume-Uni] ; Kerri Howard [États-Unis] ; Ronald Klein [États-Unis] ; Jill P. Crandall [États-Unis] ; Nir Barzilai [États-Unis] ; Sofiya Milman [États-Unis] ; Danny Ben-Avraham [États-Unis] ; Bruce H. R. Wolffenbuttel [Pays-Bas] ; Andrew D. Paterson [Canada]Source :
- Diabetologia [ 0012-186X ] ; 2014.
Abstract
Skin fluorescence (SF) is a non-invasive marker of AGEs and is associated with the long-term complications of diabetes. SF increases with age and is also greater among individuals with diabetes. A familial correlation of SF suggests that genetics may play a role. We therefore performed parallel genome-wide association studies of SF in two cohorts.
Cohort 1 included 1,082 participants, 35–67 years of age with type 1 diabetes. Cohort 2 included 8,721 participants without diabetes, aged 18–90 years.
rs1495741 was significantly associated with SF in Cohort 1 (
We identified a robust association between
The online version of this article (doi:10.1007/s00125-014-3286-9) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
Url:
DOI: 10.1007/s00125-014-3286-9
PubMed: 24934506
PubMed Central: 4079945
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Lutgers</name><affiliation wicri:level="1"><nlm:aff id="Aff2">Department of Endocrinology, University Medical Center Groningen, University of Groningen, HPC AA31, PO Box 30001, 9700 RB Groningen, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Endocrinology, University Medical Center Groningen, University of Groningen, HPC AA31, PO Box 30001, 9700 RB Groningen</wicri:regionArea><wicri:noRegion>9700 RB Groningen</wicri:noRegion></affiliation></author><author><name sortKey="Maynard, John" sort="Maynard, John" uniqKey="Maynard J" first="John" last="Maynard">John Maynard</name><affiliation wicri:level="2"><nlm:aff id="Aff3">VeraLight, Inc, Albuquerque, NM USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Nouveau-Mexique</region></placeName><wicri:cityArea>VeraLight, Inc, Albuquerque</wicri:cityArea></affiliation></author><author><name sortKey="Klein, Barbara E K" sort="Klein, Barbara E K" uniqKey="Klein B" first="Barbara E. K." last="Klein">Barbara E. K. Klein</name><affiliation wicri:level="2"><nlm:aff id="Aff4">Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Wisconsin</region></placeName><wicri:cityArea>Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison</wicri:cityArea></affiliation></author><author><name sortKey="Lee, Kristine E" sort="Lee, Kristine E" uniqKey="Lee K" first="Kristine E." last="Lee">Kristine E. Lee</name><affiliation wicri:level="2"><nlm:aff id="Aff4">Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Wisconsin</region></placeName><wicri:cityArea>Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison</wicri:cityArea></affiliation></author><author><name sortKey="Atzmon, Gil" sort="Atzmon, Gil" uniqKey="Atzmon G" first="Gil" last="Atzmon">Gil Atzmon</name><affiliation wicri:level="2"><nlm:aff id="Aff5">Department of Medicine, Institute for Aging Research and the Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY USA</nlm:aff><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Medicine, Institute for Aging Research and the Diabetes Research Center, Albert Einstein College of Medicine, Bronx</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="Aff6">Department of Genetics, Albert Einstein College of Medicine, Bronx, NY USA</nlm:aff><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Genetics, Albert Einstein College of Medicine, Bronx</wicri:cityArea></affiliation></author><author><name sortKey="Monnier, Vincent M" sort="Monnier, Vincent M" uniqKey="Monnier V" first="Vincent M." last="Monnier">Vincent M. Monnier</name><affiliation wicri:level="2"><nlm:aff id="Aff7">Department of Pathology, Case Western Reserve University, Cleveland, OH USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Ohio</region></placeName><wicri:cityArea>Department of Pathology, Case Western Reserve University, Cleveland</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="Aff8">Department of Biochemistry, Case Western Reserve University, Cleveland, OH USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Ohio</region></placeName><wicri:cityArea>Department of Biochemistry, Case Western Reserve University, Cleveland</wicri:cityArea></affiliation></author><author><name sortKey="Van Vliet Ostaptchouk, Jana V" sort="Van Vliet Ostaptchouk, Jana V" uniqKey="Van Vliet Ostaptchouk J" first="Jana V." last="Van Vliet-Ostaptchouk">Jana V. Van Vliet-Ostaptchouk</name><affiliation wicri:level="1"><nlm:aff id="Aff2">Department of Endocrinology, University Medical Center Groningen, University of Groningen, HPC AA31, PO Box 30001, 9700 RB Groningen, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Endocrinology, University Medical Center Groningen, University of Groningen, HPC AA31, PO Box 30001, 9700 RB Groningen</wicri:regionArea><wicri:noRegion>9700 RB Groningen</wicri:noRegion></affiliation></author><author><name sortKey="Graaff, Reindert" sort="Graaff, Reindert" uniqKey="Graaff R" first="Reindert" last="Graaff">Reindert Graaff</name><affiliation wicri:level="1"><nlm:aff id="Aff2">Department of Endocrinology, University Medical Center Groningen, University of Groningen, HPC AA31, PO Box 30001, 9700 RB Groningen, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Endocrinology, University Medical Center Groningen, University of Groningen, HPC AA31, PO Box 30001, 9700 RB Groningen</wicri:regionArea><wicri:noRegion>9700 RB Groningen</wicri:noRegion></affiliation></author><author><name sortKey="Van Der Harst, Pim" sort="Van Der Harst, Pim" uniqKey="Van Der Harst P" first="Pim" last="Van Der Harst">Pim Van Der Harst</name><affiliation wicri:level="3"><nlm:aff id="Aff9">Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen</wicri:regionArea><placeName><settlement type="city">Groningue</settlement><region nuts="2" type="province">Groningue (province)</region></placeName></affiliation></author><author><name sortKey="Snieder, Harold" sort="Snieder, Harold" uniqKey="Snieder H" first="Harold" last="Snieder">Harold Snieder</name><affiliation wicri:level="3"><nlm:aff id="Aff10">Unit of Genetic Epidemiology and Bioinformatics, Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Unit of Genetic Epidemiology and Bioinformatics, Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen</wicri:regionArea><placeName><settlement type="city">Groningue</settlement><region nuts="2" type="province">Groningue (province)</region></placeName></affiliation></author><author><name sortKey="Van Der Klauw, Melanie M" sort="Van Der Klauw, Melanie M" uniqKey="Van Der Klauw M" first="Melanie M." last="Van Der Klauw">Melanie M. Van Der Klauw</name><affiliation wicri:level="1"><nlm:aff id="Aff2">Department of Endocrinology, University Medical Center Groningen, University of Groningen, HPC AA31, PO Box 30001, 9700 RB Groningen, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Endocrinology, University Medical Center Groningen, University of Groningen, HPC AA31, PO Box 30001, 9700 RB Groningen</wicri:regionArea><wicri:noRegion>9700 RB Groningen</wicri:noRegion></affiliation></author><author><name sortKey="Sell, David R" sort="Sell, David R" uniqKey="Sell D" first="David R." last="Sell">David R. Sell</name><affiliation wicri:level="2"><nlm:aff id="Aff7">Department of Pathology, Case Western Reserve University, Cleveland, OH USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Ohio</region></placeName><wicri:cityArea>Department of Pathology, Case Western Reserve University, Cleveland</wicri:cityArea></affiliation></author><author><name sortKey="Hosseini, S Mohsen" sort="Hosseini, S Mohsen" uniqKey="Hosseini S" first="S. Mohsen" last="Hosseini">S. Mohsen Hosseini</name><affiliation><nlm:aff id="Aff1">Program in Genetics and Genomic Biology, Hospital for Sick Children, 686 Bay Street, Room 12.9830, Toronto, ON M5G 0A4 Canada</nlm:aff><wicri:noCountry code="subfield">ON M5G 0A4 Canada</wicri:noCountry></affiliation></author><author><name sortKey="Cleary, Patricia A" sort="Cleary, Patricia A" uniqKey="Cleary P" first="Patricia A." last="Cleary">Patricia A. Cleary</name><affiliation wicri:level="2"><nlm:aff id="Aff11">Biostatistics Center, George Washington University, Rockville, MD USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Biostatistics Center, George Washington University, Rockville</wicri:cityArea></affiliation></author><author><name sortKey="Braffett, Barbara H" sort="Braffett, Barbara H" uniqKey="Braffett B" first="Barbara H." last="Braffett">Barbara H. Braffett</name><affiliation wicri:level="2"><nlm:aff id="Aff11">Biostatistics Center, George Washington University, Rockville, MD USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Biostatistics Center, George Washington University, Rockville</wicri:cityArea></affiliation></author><author><name sortKey="Orchard, Trevor J" sort="Orchard, Trevor J" uniqKey="Orchard T" first="Trevor J." last="Orchard">Trevor J. Orchard</name><affiliation wicri:level="2"><nlm:aff id="Aff12">Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Department of Epidemiology, University of Pittsburgh, Pittsburgh</wicri:cityArea></affiliation></author><author><name sortKey="Lyons, Timothy J" sort="Lyons, Timothy J" uniqKey="Lyons T" first="Timothy J." last="Lyons">Timothy J. Lyons</name><affiliation wicri:level="1"><nlm:aff id="Aff13">Centre for Experimental Medicine, Institute of Clinical Science, Queen’s University of Belfast, Belfast, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Centre for Experimental Medicine, Institute of Clinical Science, Queen’s University of Belfast, Belfast</wicri:regionArea><wicri:noRegion>Belfast</wicri:noRegion></affiliation></author><author><name sortKey="Howard, Kerri" sort="Howard, Kerri" uniqKey="Howard K" first="Kerri" last="Howard">Kerri Howard</name><affiliation wicri:level="2"><nlm:aff id="Aff4">Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Wisconsin</region></placeName><wicri:cityArea>Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison</wicri:cityArea></affiliation></author><author><name sortKey="Klein, Ronald" sort="Klein, Ronald" uniqKey="Klein R" first="Ronald" last="Klein">Ronald Klein</name><affiliation wicri:level="2"><nlm:aff id="Aff4">Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Wisconsin</region></placeName><wicri:cityArea>Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison</wicri:cityArea></affiliation></author><author><name sortKey="Crandall, Jill P" sort="Crandall, Jill P" uniqKey="Crandall J" first="Jill P." last="Crandall">Jill P. Crandall</name><affiliation wicri:level="2"><nlm:aff id="Aff5">Department of Medicine, Institute for Aging Research and the Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY USA</nlm:aff><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Medicine, Institute for Aging Research and the Diabetes Research Center, Albert Einstein College of Medicine, Bronx</wicri:cityArea></affiliation></author><author><name sortKey="Barzilai, Nir" sort="Barzilai, Nir" uniqKey="Barzilai N" first="Nir" last="Barzilai">Nir Barzilai</name><affiliation wicri:level="2"><nlm:aff id="Aff5">Department of Medicine, Institute for Aging Research and the Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY USA</nlm:aff><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Medicine, Institute for Aging Research and the Diabetes Research Center, Albert Einstein College of Medicine, Bronx</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="Aff6">Department of Genetics, Albert Einstein College of Medicine, Bronx, NY USA</nlm:aff><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Genetics, Albert Einstein College of Medicine, Bronx</wicri:cityArea></affiliation></author><author><name sortKey="Milman, Sofiya" sort="Milman, Sofiya" uniqKey="Milman S" first="Sofiya" last="Milman">Sofiya Milman</name><affiliation wicri:level="2"><nlm:aff id="Aff5">Department of Medicine, Institute for Aging Research and the Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY USA</nlm:aff><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Medicine, Institute for Aging Research and the Diabetes Research Center, Albert Einstein College of Medicine, Bronx</wicri:cityArea></affiliation></author><author><name sortKey="Ben Avraham, Danny" sort="Ben Avraham, Danny" uniqKey="Ben Avraham D" first="Danny" last="Ben-Avraham">Danny Ben-Avraham</name><affiliation wicri:level="2"><nlm:aff id="Aff5">Department of Medicine, Institute for Aging Research and the Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY USA</nlm:aff><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Medicine, Institute for Aging Research and the Diabetes Research Center, Albert Einstein College of Medicine, Bronx</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="Aff6">Department of Genetics, Albert Einstein College of Medicine, Bronx, NY USA</nlm:aff><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Genetics, Albert Einstein College of Medicine, Bronx</wicri:cityArea></affiliation></author><author><name sortKey="Wolffenbuttel, Bruce H R" sort="Wolffenbuttel, Bruce H R" uniqKey="Wolffenbuttel B" first="Bruce H. R." last="Wolffenbuttel">Bruce H. R. Wolffenbuttel</name><affiliation wicri:level="1"><nlm:aff id="Aff2">Department of Endocrinology, University Medical Center Groningen, University of Groningen, HPC AA31, PO Box 30001, 9700 RB Groningen, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Endocrinology, University Medical Center Groningen, University of Groningen, HPC AA31, PO Box 30001, 9700 RB Groningen</wicri:regionArea><wicri:noRegion>9700 RB Groningen</wicri:noRegion></affiliation></author><author><name sortKey="Paterson, Andrew D" sort="Paterson, Andrew D" uniqKey="Paterson A" first="Andrew D." last="Paterson">Andrew D. Paterson</name><affiliation><nlm:aff id="Aff1">Program in Genetics and Genomic Biology, Hospital for Sick Children, 686 Bay Street, Room 12.9830, Toronto, ON M5G 0A4 Canada</nlm:aff><wicri:noCountry code="subfield">ON M5G 0A4 Canada</wicri:noCountry></affiliation><affiliation wicri:level="4"><nlm:aff id="Aff14">Dalla Lana School of Public Health, University of Toronto, Toronto, ON Canada</nlm:aff><orgName type="university">Université de Toronto</orgName><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24934506</idno><idno type="pmc">4079945</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4079945</idno><idno type="RBID">PMC:4079945</idno><idno type="doi">10.1007/s00125-014-3286-9</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">000470</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000470</idno><idno type="wicri:Area/Pmc/Curation">000469</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000469</idno><idno type="wicri:Area/Pmc/Checkpoint">001250</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">001250</idno><idno type="wicri:Area/Ncbi/Merge">002569</idno><idno type="wicri:Area/Ncbi/Curation">002569</idno><idno type="wicri:Area/Ncbi/Checkpoint">002569</idno><idno type="wicri:doubleKey">0012-186X:2014:Eny K:gwas:identifies:an</idno><idno type="wicri:Area/Main/Merge">002D98</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">GWAS identifies an <italic>NAT2</italic> acetylator status tag single nucleotide polymorphism to be a major locus for skin fluorescence</title><author><name sortKey="Eny, Karen M" sort="Eny, Karen M" uniqKey="Eny K" first="Karen M." last="Eny">Karen M. Eny</name><affiliation><nlm:aff id="Aff1">Program in Genetics and Genomic Biology, Hospital for Sick Children, 686 Bay Street, Room 12.9830, Toronto, ON M5G 0A4 Canada</nlm:aff><wicri:noCountry code="subfield">ON M5G 0A4 Canada</wicri:noCountry></affiliation></author><author><name sortKey="Lutgers, Helen L" sort="Lutgers, Helen L" uniqKey="Lutgers H" first="Helen L." last="Lutgers">Helen L. Lutgers</name><affiliation wicri:level="1"><nlm:aff id="Aff2">Department of Endocrinology, University Medical Center Groningen, University of Groningen, HPC AA31, PO Box 30001, 9700 RB Groningen, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Endocrinology, University Medical Center Groningen, University of Groningen, HPC AA31, PO Box 30001, 9700 RB Groningen</wicri:regionArea><wicri:noRegion>9700 RB Groningen</wicri:noRegion></affiliation></author><author><name sortKey="Maynard, John" sort="Maynard, John" uniqKey="Maynard J" first="John" last="Maynard">John Maynard</name><affiliation wicri:level="2"><nlm:aff id="Aff3">VeraLight, Inc, Albuquerque, NM USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Nouveau-Mexique</region></placeName><wicri:cityArea>VeraLight, Inc, Albuquerque</wicri:cityArea></affiliation></author><author><name sortKey="Klein, Barbara E K" sort="Klein, Barbara E K" uniqKey="Klein B" first="Barbara E. K." last="Klein">Barbara E. K. Klein</name><affiliation wicri:level="2"><nlm:aff id="Aff4">Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Wisconsin</region></placeName><wicri:cityArea>Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison</wicri:cityArea></affiliation></author><author><name sortKey="Lee, Kristine E" sort="Lee, Kristine E" uniqKey="Lee K" first="Kristine E." last="Lee">Kristine E. Lee</name><affiliation wicri:level="2"><nlm:aff id="Aff4">Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Wisconsin</region></placeName><wicri:cityArea>Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison</wicri:cityArea></affiliation></author><author><name sortKey="Atzmon, Gil" sort="Atzmon, Gil" uniqKey="Atzmon G" first="Gil" last="Atzmon">Gil Atzmon</name><affiliation wicri:level="2"><nlm:aff id="Aff5">Department of Medicine, Institute for Aging Research and the Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY USA</nlm:aff><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Medicine, Institute for Aging Research and the Diabetes Research Center, Albert Einstein College of Medicine, Bronx</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="Aff6">Department of Genetics, Albert Einstein College of Medicine, Bronx, NY USA</nlm:aff><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Genetics, Albert Einstein College of Medicine, Bronx</wicri:cityArea></affiliation></author><author><name sortKey="Monnier, Vincent M" sort="Monnier, Vincent M" uniqKey="Monnier V" first="Vincent M." last="Monnier">Vincent M. Monnier</name><affiliation wicri:level="2"><nlm:aff id="Aff7">Department of Pathology, Case Western Reserve University, Cleveland, OH USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Ohio</region></placeName><wicri:cityArea>Department of Pathology, Case Western Reserve University, Cleveland</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="Aff8">Department of Biochemistry, Case Western Reserve University, Cleveland, OH USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Ohio</region></placeName><wicri:cityArea>Department of Biochemistry, Case Western Reserve University, Cleveland</wicri:cityArea></affiliation></author><author><name sortKey="Van Vliet Ostaptchouk, Jana V" sort="Van Vliet Ostaptchouk, Jana V" uniqKey="Van Vliet Ostaptchouk J" first="Jana V." last="Van Vliet-Ostaptchouk">Jana V. Van Vliet-Ostaptchouk</name><affiliation wicri:level="1"><nlm:aff id="Aff2">Department of Endocrinology, University Medical Center Groningen, University of Groningen, HPC AA31, PO Box 30001, 9700 RB Groningen, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Endocrinology, University Medical Center Groningen, University of Groningen, HPC AA31, PO Box 30001, 9700 RB Groningen</wicri:regionArea><wicri:noRegion>9700 RB Groningen</wicri:noRegion></affiliation></author><author><name sortKey="Graaff, Reindert" sort="Graaff, Reindert" uniqKey="Graaff R" first="Reindert" last="Graaff">Reindert Graaff</name><affiliation wicri:level="1"><nlm:aff id="Aff2">Department of Endocrinology, University Medical Center Groningen, University of Groningen, HPC AA31, PO Box 30001, 9700 RB Groningen, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Endocrinology, University Medical Center Groningen, University of Groningen, HPC AA31, PO Box 30001, 9700 RB Groningen</wicri:regionArea><wicri:noRegion>9700 RB Groningen</wicri:noRegion></affiliation></author><author><name sortKey="Van Der Harst, Pim" sort="Van Der Harst, Pim" uniqKey="Van Der Harst P" first="Pim" last="Van Der Harst">Pim Van Der Harst</name><affiliation wicri:level="3"><nlm:aff id="Aff9">Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen</wicri:regionArea><placeName><settlement type="city">Groningue</settlement><region nuts="2" type="province">Groningue (province)</region></placeName></affiliation></author><author><name sortKey="Snieder, Harold" sort="Snieder, Harold" uniqKey="Snieder H" first="Harold" last="Snieder">Harold Snieder</name><affiliation wicri:level="3"><nlm:aff id="Aff10">Unit of Genetic Epidemiology and Bioinformatics, Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Unit of Genetic Epidemiology and Bioinformatics, Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen</wicri:regionArea><placeName><settlement type="city">Groningue</settlement><region nuts="2" type="province">Groningue (province)</region></placeName></affiliation></author><author><name sortKey="Van Der Klauw, Melanie M" sort="Van Der Klauw, Melanie M" uniqKey="Van Der Klauw M" first="Melanie M." last="Van Der Klauw">Melanie M. Van Der Klauw</name><affiliation wicri:level="1"><nlm:aff id="Aff2">Department of Endocrinology, University Medical Center Groningen, University of Groningen, HPC AA31, PO Box 30001, 9700 RB Groningen, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Endocrinology, University Medical Center Groningen, University of Groningen, HPC AA31, PO Box 30001, 9700 RB Groningen</wicri:regionArea><wicri:noRegion>9700 RB Groningen</wicri:noRegion></affiliation></author><author><name sortKey="Sell, David R" sort="Sell, David R" uniqKey="Sell D" first="David R." last="Sell">David R. Sell</name><affiliation wicri:level="2"><nlm:aff id="Aff7">Department of Pathology, Case Western Reserve University, Cleveland, OH USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Ohio</region></placeName><wicri:cityArea>Department of Pathology, Case Western Reserve University, Cleveland</wicri:cityArea></affiliation></author><author><name sortKey="Hosseini, S Mohsen" sort="Hosseini, S Mohsen" uniqKey="Hosseini S" first="S. Mohsen" last="Hosseini">S. Mohsen Hosseini</name><affiliation><nlm:aff id="Aff1">Program in Genetics and Genomic Biology, Hospital for Sick Children, 686 Bay Street, Room 12.9830, Toronto, ON M5G 0A4 Canada</nlm:aff><wicri:noCountry code="subfield">ON M5G 0A4 Canada</wicri:noCountry></affiliation></author><author><name sortKey="Cleary, Patricia A" sort="Cleary, Patricia A" uniqKey="Cleary P" first="Patricia A." last="Cleary">Patricia A. Cleary</name><affiliation wicri:level="2"><nlm:aff id="Aff11">Biostatistics Center, George Washington University, Rockville, MD USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Biostatistics Center, George Washington University, Rockville</wicri:cityArea></affiliation></author><author><name sortKey="Braffett, Barbara H" sort="Braffett, Barbara H" uniqKey="Braffett B" first="Barbara H." last="Braffett">Barbara H. Braffett</name><affiliation wicri:level="2"><nlm:aff id="Aff11">Biostatistics Center, George Washington University, Rockville, MD USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Biostatistics Center, George Washington University, Rockville</wicri:cityArea></affiliation></author><author><name sortKey="Orchard, Trevor J" sort="Orchard, Trevor J" uniqKey="Orchard T" first="Trevor J." last="Orchard">Trevor J. Orchard</name><affiliation wicri:level="2"><nlm:aff id="Aff12">Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Department of Epidemiology, University of Pittsburgh, Pittsburgh</wicri:cityArea></affiliation></author><author><name sortKey="Lyons, Timothy J" sort="Lyons, Timothy J" uniqKey="Lyons T" first="Timothy J." last="Lyons">Timothy J. Lyons</name><affiliation wicri:level="1"><nlm:aff id="Aff13">Centre for Experimental Medicine, Institute of Clinical Science, Queen’s University of Belfast, Belfast, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Centre for Experimental Medicine, Institute of Clinical Science, Queen’s University of Belfast, Belfast</wicri:regionArea><wicri:noRegion>Belfast</wicri:noRegion></affiliation></author><author><name sortKey="Howard, Kerri" sort="Howard, Kerri" uniqKey="Howard K" first="Kerri" last="Howard">Kerri Howard</name><affiliation wicri:level="2"><nlm:aff id="Aff4">Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Wisconsin</region></placeName><wicri:cityArea>Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison</wicri:cityArea></affiliation></author><author><name sortKey="Klein, Ronald" sort="Klein, Ronald" uniqKey="Klein R" first="Ronald" last="Klein">Ronald Klein</name><affiliation wicri:level="2"><nlm:aff id="Aff4">Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Wisconsin</region></placeName><wicri:cityArea>Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison</wicri:cityArea></affiliation></author><author><name sortKey="Crandall, Jill P" sort="Crandall, Jill P" uniqKey="Crandall J" first="Jill P." last="Crandall">Jill P. Crandall</name><affiliation wicri:level="2"><nlm:aff id="Aff5">Department of Medicine, Institute for Aging Research and the Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY USA</nlm:aff><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Medicine, Institute for Aging Research and the Diabetes Research Center, Albert Einstein College of Medicine, Bronx</wicri:cityArea></affiliation></author><author><name sortKey="Barzilai, Nir" sort="Barzilai, Nir" uniqKey="Barzilai N" first="Nir" last="Barzilai">Nir Barzilai</name><affiliation wicri:level="2"><nlm:aff id="Aff5">Department of Medicine, Institute for Aging Research and the Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY USA</nlm:aff><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Medicine, Institute for Aging Research and the Diabetes Research Center, Albert Einstein College of Medicine, Bronx</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="Aff6">Department of Genetics, Albert Einstein College of Medicine, Bronx, NY USA</nlm:aff><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Genetics, Albert Einstein College of Medicine, Bronx</wicri:cityArea></affiliation></author><author><name sortKey="Milman, Sofiya" sort="Milman, Sofiya" uniqKey="Milman S" first="Sofiya" last="Milman">Sofiya Milman</name><affiliation wicri:level="2"><nlm:aff id="Aff5">Department of Medicine, Institute for Aging Research and the Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY USA</nlm:aff><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Medicine, Institute for Aging Research and the Diabetes Research Center, Albert Einstein College of Medicine, Bronx</wicri:cityArea></affiliation></author><author><name sortKey="Ben Avraham, Danny" sort="Ben Avraham, Danny" uniqKey="Ben Avraham D" first="Danny" last="Ben-Avraham">Danny Ben-Avraham</name><affiliation wicri:level="2"><nlm:aff id="Aff5">Department of Medicine, Institute for Aging Research and the Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY USA</nlm:aff><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Medicine, Institute for Aging Research and the Diabetes Research Center, Albert Einstein College of Medicine, Bronx</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="Aff6">Department of Genetics, Albert Einstein College of Medicine, Bronx, NY USA</nlm:aff><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Genetics, Albert Einstein College of Medicine, Bronx</wicri:cityArea></affiliation></author><author><name sortKey="Wolffenbuttel, Bruce H R" sort="Wolffenbuttel, Bruce H R" uniqKey="Wolffenbuttel B" first="Bruce H. R." last="Wolffenbuttel">Bruce H. R. Wolffenbuttel</name><affiliation wicri:level="1"><nlm:aff id="Aff2">Department of Endocrinology, University Medical Center Groningen, University of Groningen, HPC AA31, PO Box 30001, 9700 RB Groningen, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Endocrinology, University Medical Center Groningen, University of Groningen, HPC AA31, PO Box 30001, 9700 RB Groningen</wicri:regionArea><wicri:noRegion>9700 RB Groningen</wicri:noRegion></affiliation></author><author><name sortKey="Paterson, Andrew D" sort="Paterson, Andrew D" uniqKey="Paterson A" first="Andrew D." last="Paterson">Andrew D. Paterson</name><affiliation><nlm:aff id="Aff1">Program in Genetics and Genomic Biology, Hospital for Sick Children, 686 Bay Street, Room 12.9830, Toronto, ON M5G 0A4 Canada</nlm:aff><wicri:noCountry code="subfield">ON M5G 0A4 Canada</wicri:noCountry></affiliation><affiliation wicri:level="4"><nlm:aff id="Aff14">Dalla Lana School of Public Health, University of Toronto, Toronto, ON Canada</nlm:aff><orgName type="university">Université de Toronto</orgName><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author></analytic><series><title level="j">Diabetologia</title><idno type="ISSN">0012-186X</idno><idno type="eISSN">1432-0428</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Aims/hypothesis</title><p>Skin fluorescence (SF) is a non-invasive marker of AGEs and is associated with the long-term complications of diabetes. SF increases with age and is also greater among individuals with diabetes. A familial correlation of SF suggests that genetics may play a role. We therefore performed parallel genome-wide association studies of SF in two cohorts.</p></sec><sec><title>Methods</title><p>Cohort 1 included 1,082 participants, 35–67 years of age with type 1 diabetes. Cohort 2 included 8,721 participants without diabetes, aged 18–90 years.</p></sec><sec><title>Results</title><p>rs1495741 was significantly associated with SF in Cohort 1 (<italic>p</italic> < 6 × 10<sup>−10</sup>), which is known to tag the <italic>NAT2</italic> acetylator phenotype. The fast acetylator genotype was associated with lower SF, explaining up to 15% of the variance. In Cohort 2, the top signal associated with SF (<italic>p</italic> = 8.3 × 10<sup>−42</sup>) was rs4921914, also in <italic>NAT2</italic>, 440 bases upstream of rs1495741 (linkage disequilibrium <italic>r</italic><sup>2</sup> = 1.0 for rs4921914 with rs1495741). We replicated these results in two additional cohorts, one with and one without type 1 diabetes. Finally, to understand which compounds are contributing to the <italic>NAT2</italic>–SF signal, we examined 11 compounds assayed from skin biopsies (<italic>n</italic> = 198): the fast acetylator genotype was associated with lower levels of the AGEs hydroimidazolones of glyoxal (<italic>p</italic> = 0.017).</p></sec><sec><title>Conclusions/interpretation</title><p>We identified a robust association between <italic>NAT2</italic> and SF in people with and without diabetes. Our findings provide proof of principle that genetic variation contributes to interindividual SF and that <italic>NAT2</italic> acetylation status plays a major role.</p></sec><sec><title>Electronic supplementary material</title><p>The online version of this article (doi:10.1007/s00125-014-3286-9) contains peer-reviewed but unedited supplementary material, which is available to authorised users.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Dyer, Dg" uniqKey="Dyer D">DG Dyer</name></author><author><name sortKey="Dunn, Ja" uniqKey="Dunn J">JA Dunn</name></author><author><name sortKey="Thorpe, Sr" uniqKey="Thorpe S">SR Thorpe</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brownlee, M" uniqKey="Brownlee M">M Brownlee</name></author><author><name sortKey="Cerami, A" uniqKey="Cerami A">A Cerami</name></author><author><name sortKey="Vlassara, H" uniqKey="Vlassara H">H 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Chatterjee</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Suhre, K" uniqKey="Suhre K">K Suhre</name></author><author><name sortKey="Shin, Sy" uniqKey="Shin S">SY Shin</name></author><author><name sortKey="Petersen, Ak" uniqKey="Petersen A">AK Petersen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Suhre, K" uniqKey="Suhre K">K Suhre</name></author><author><name sortKey="Wallaschofski, H" uniqKey="Wallaschofski H">H Wallaschofski</name></author><author><name sortKey="Raffler, J" uniqKey="Raffler J">J Raffler</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Varani, J" uniqKey="Varani J">J Varani</name></author><author><name sortKey="Dame, Mk" uniqKey="Dame M">MK Dame</name></author><author><name sortKey="Rittie, L" uniqKey="Rittie L">L Rittie</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bhaiya, P" uniqKey="Bhaiya P">P Bhaiya</name></author><author><name sortKey="Roychowdhury, S" uniqKey="Roychowdhury S">S Roychowdhury</name></author><author><name sortKey="Vyas, Pm" uniqKey="Vyas P">PM Vyas</name></author><author><name sortKey="Doll, Ma" uniqKey="Doll M">MA Doll</name></author><author><name sortKey="Hein, Dw" uniqKey="Hein D">DW Hein</name></author><author><name sortKey="Svensson, Ck" uniqKey="Svensson C">CK Svensson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hickman, D" uniqKey="Hickman D">D Hickman</name></author><author><name sortKey="Pope, J" uniqKey="Pope J">J Pope</name></author><author><name sortKey="Patil, Sd" uniqKey="Patil S">SD Patil</name></author></analytic></biblStruct></listBibl></div1></back></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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