LymphedemaV1, Main, Exploration, bibRecord, 004267

HLA Class II Locus and Susceptibility to Podoconiosis

Identifieur interne : 004267 ( Main/Exploration ); précédent : 004266; suivant : 004268

HLA Class II Locus and Susceptibility to Podoconiosis

Auteurs : Fasil Tekola Ayele ; Adebowale Adeyemo ; Chris Finan ; Elena Hailu ; Paul Sinnott ; Natalia Diaz Burlinson ; Abraham Aseffa ; Charles N. Rotimi ; Melanie J. Newport ; Gail Davey

Source :

The New England Journal of Medicine [ 0028-4793 ] ; 2012.

RBID : PMC:3350841

Descripteurs français

KwdFr :
- Adulte, Adulte d'âge moyen, Allèles, Chaines alpha des antigènes HLA-DQ (génétique), Femelle, Gènes MHC de classe II, Génotype, Humains, Maladies endémiques, Mâle, Polymorphisme de nucléotide simple, Prédisposition génétique à une maladie, Test d'histocompatibilité, Éléphantiasis (génétique), Éléphantiasis (épidémiologie), Éthiopie, Étude d'association pangénomique, Études cas-témoins.
MESH :
- génétique : Chaines alpha des antigènes HLA-DQ, Éléphantiasis.
- épidémiologie : Éléphantiasis.
- Adulte, Adulte d'âge moyen, Allèles, Femelle, Gènes MHC de classe II, Génotype, Humains, Maladies endémiques, Mâle, Polymorphisme de nucléotide simple, Prédisposition génétique à une maladie, Test d'histocompatibilité, Éthiopie, Étude d'association pangénomique, Études cas-témoins.
Wicri :
- geographic : Éthiopie.

English descriptors

KwdEn :
- Adult, Alleles, Case-Control Studies, Elephantiasis (epidemiology), Elephantiasis (genetics), Endemic Diseases, Ethiopia, Female, Genes, MHC Class II, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, HLA-DQ alpha-Chains (genetics), Histocompatibility Testing, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide.
MESH :
- chemical , genetics : HLA-DQ alpha-Chains.
- geographic : Ethiopia.
- epidemiology : Elephantiasis.
- genetics : Elephantiasis.
- Adult, Alleles, Case-Control Studies, Endemic Diseases, Female, Genes, MHC Class II, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Histocompatibility Testing, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide.

Abstract

BACKGROUND

Podoconiosis is a tropical lymphedema resulting from long-term barefoot exposure to red-clay soil derived from volcanic rock. The World Health Organization recently designated it as a neglected tropical disease. Podoconiosis develops in only a subgroup of exposed people, and studies have shown familial clustering with high heritability (63%).

METHODS

We conducted a genomewide association study of 194 case patients and 203 controls from southern Ethiopia. Findings were validated by means of family-based association testing in 202 family trios and HLA typing in 94 case patients and 94 controls.

RESULTS

We found a genomewide significant association of podoconiosis with the single-nucleotide polymorphism (SNP) rs17612858, located 5.8 kb from the HLA-DQA1 locus (in the allelic model: odds ratio, 2.44; 95% confidence interval [CI], 1.82 to 3.26; P = 1.42×10⁻⁹; and in the additive model: odds ratio, 2.19; 95% CI, 1.66 to 2.90; P = 3.44×10⁻⁸), and suggestive associations (P<1.0×10⁻⁵) with seven other SNPs in or near HLA-DQB1, HLA-DQA1, and HLA-DRB1. We confirmed these associations using family-based association testing. HLA typing showed the alleles HLA-DRB1*0701 (odds ratio, 2.00), DQA1*0201 (odds ratio, 1.91), and DQB1*0202 (odds ratio, 1.79) and the HLA-DRB1*0701–DQB1*0202 haplotype (odds ratio, 1.92) were risk variants for podoconiosis.

CONCLUSIONS

Association between variants in HLA class II loci with podoconiosis (a noncommuni-cable disease) suggests that the condition may be a T-cell–mediated inflammatory disease and is a model for gene–environment interactions that may be relevant to other complex genetic disorders. (Funded by the Wellcome Trust and others.)

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3350841

DOI: 10.1056/NEJMoa1108448
PubMed: 22455414
PubMed Central: 3350841

Affiliations:

Le document en format XML

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<term>Alleles</term>
<term>Case-Control Studies</term>
<term>Elephantiasis (epidemiology)</term>
<term>Elephantiasis (genetics)</term>
<term>Endemic Diseases</term>
<term>Ethiopia</term>
<term>Female</term>
<term>Genes, MHC Class II</term>
<term>Genetic Predisposition to Disease</term>
<term>Genome-Wide Association Study</term>
<term>Genotype</term>
<term>HLA-DQ alpha-Chains (genetics)</term>
<term>Histocompatibility Testing</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Polymorphism, Single Nucleotide</term>
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<keywords scheme="KwdFr" xml:lang="fr"><term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Allèles</term>
<term>Chaines alpha des antigènes HLA-DQ (génétique)</term>
<term>Femelle</term>
<term>Gènes MHC de classe II</term>
<term>Génotype</term>
<term>Humains</term>
<term>Maladies endémiques</term>
<term>Mâle</term>
<term>Polymorphisme de nucléotide simple</term>
<term>Prédisposition génétique à une maladie</term>
<term>Test d'histocompatibilité</term>
<term>Éléphantiasis (génétique)</term>
<term>Éléphantiasis (épidémiologie)</term>
<term>Éthiopie</term>
<term>Étude d'association pangénomique</term>
<term>Études cas-témoins</term>
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<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>HLA-DQ alpha-Chains</term>
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<keywords scheme="MESH" type="geographic" xml:lang="en"><term>Ethiopia</term>
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<keywords scheme="MESH" qualifier="epidemiology" xml:lang="en"><term>Elephantiasis</term>
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<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Elephantiasis</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Chaines alpha des antigènes HLA-DQ</term>
<term>Éléphantiasis</term>
</keywords>
<keywords scheme="MESH" qualifier="épidémiologie" xml:lang="fr"><term>Éléphantiasis</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Adult</term>
<term>Alleles</term>
<term>Case-Control Studies</term>
<term>Endemic Diseases</term>
<term>Female</term>
<term>Genes, MHC Class II</term>
<term>Genetic Predisposition to Disease</term>
<term>Genome-Wide Association Study</term>
<term>Genotype</term>
<term>Histocompatibility Testing</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Polymorphism, Single Nucleotide</term>
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<term>Adulte d'âge moyen</term>
<term>Allèles</term>
<term>Femelle</term>
<term>Gènes MHC de classe II</term>
<term>Génotype</term>
<term>Humains</term>
<term>Maladies endémiques</term>
<term>Mâle</term>
<term>Polymorphisme de nucléotide simple</term>
<term>Prédisposition génétique à une maladie</term>
<term>Test d'histocompatibilité</term>
<term>Éthiopie</term>
<term>Étude d'association pangénomique</term>
<term>Études cas-témoins</term>
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<front><div type="abstract" xml:lang="en"><sec id="S1"><title>BACKGROUND</title>
<p id="P1">Podoconiosis is a tropical lymphedema resulting from long-term barefoot exposure to red-clay soil derived from volcanic rock. The World Health Organization recently designated it as a neglected tropical disease. Podoconiosis develops in only a subgroup of exposed people, and studies have shown familial clustering with high heritability (63%).</p>
</sec>
<sec id="S2"><title>METHODS</title>
<p id="P2">We conducted a genomewide association study of 194 case patients and 203 controls from southern Ethiopia. Findings were validated by means of family-based association testing in 202 family trios and HLA typing in 94 case patients and 94 controls.</p>
</sec>
<sec id="S3"><title>RESULTS</title>
<p id="P3">We found a genomewide significant association of podoconiosis with the single-nucleotide polymorphism (SNP) rs17612858, located 5.8 kb from the <italic>HLA-DQA1</italic>
 locus (in the allelic model: odds ratio, 2.44; 95% confidence interval [CI], 1.82 to 3.26; P = 1.42×10<sup>−9</sup>
; and in the additive model: odds ratio, 2.19; 95% CI, 1.66 to 2.90; P = 3.44×10<sup>−8</sup>
), and suggestive associations (P<1.0×10<sup>−5</sup>
) with seven other SNPs in or near <italic>HLA-DQB1, HLA-DQA1,</italic>
 and <italic>HLA-DRB1</italic>
. We confirmed these associations using family-based association testing. HLA typing showed the alleles <italic>HLA-DRB1*0701</italic>
 (odds ratio, 2.00), <italic>DQA1*0201</italic>
 (odds ratio, 1.91), and <italic>DQB1*0202</italic>
 (odds ratio, 1.79) and the <italic>HLA-DRB1*0701–DQB1*0202</italic>
 haplotype (odds ratio, 1.92) were risk variants for podoconiosis.</p>
</sec>
<sec id="S4"><title>CONCLUSIONS</title>
<p id="P4">Association between variants in HLA class II loci with podoconiosis (a noncommuni-cable disease) suggests that the condition may be a T-cell–mediated inflammatory disease and is a model for gene–environment interactions that may be relevant to other complex genetic disorders. (Funded by the Wellcome Trust and others.)</p>
</sec>
</div>
</front>
</TEI>
<affiliations><list></list>
<tree><noCountry><name sortKey="Adeyemo, Adebowale" sort="Adeyemo, Adebowale" uniqKey="Adeyemo A" first="Adebowale" last="Adeyemo">Adebowale Adeyemo</name>
<name sortKey="Aseffa, Abraham" sort="Aseffa, Abraham" uniqKey="Aseffa A" first="Abraham" last="Aseffa">Abraham Aseffa</name>
<name sortKey="Ayele, Fasil Tekola" sort="Ayele, Fasil Tekola" uniqKey="Ayele F" first="Fasil Tekola" last="Ayele">Fasil Tekola Ayele</name>
<name sortKey="Burlinson, Natalia Diaz" sort="Burlinson, Natalia Diaz" uniqKey="Burlinson N" first="Natalia Diaz" last="Burlinson">Natalia Diaz Burlinson</name>
<name sortKey="Davey, Gail" sort="Davey, Gail" uniqKey="Davey G" first="Gail" last="Davey">Gail Davey</name>
<name sortKey="Finan, Chris" sort="Finan, Chris" uniqKey="Finan C" first="Chris" last="Finan">Chris Finan</name>
<name sortKey="Hailu, Elena" sort="Hailu, Elena" uniqKey="Hailu E" first="Elena" last="Hailu">Elena Hailu</name>
<name sortKey="Newport, Melanie J" sort="Newport, Melanie J" uniqKey="Newport M" first="Melanie J." last="Newport">Melanie J. Newport</name>
<name sortKey="Rotimi, Charles N" sort="Rotimi, Charles N" uniqKey="Rotimi C" first="Charles N." last="Rotimi">Charles N. Rotimi</name>
<name sortKey="Sinnott, Paul" sort="Sinnott, Paul" uniqKey="Sinnott P" first="Paul" last="Sinnott">Paul Sinnott</name>
</noCountry>
</tree>
</affiliations>
</record>

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Serveur d'exploration sur le lymphœdème

HLA Class II Locus and Susceptibility to Podoconiosis

HLA Class II Locus and Susceptibility to Podoconiosis

Source :

Descripteurs français

English descriptors

Abstract

Links toward previous steps (curation, corpus...)

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri

Pour générer des pages wiki

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