HLA Class II Locus and Susceptibility to Podoconiosis
Identifieur interne : 004940 ( Main/Exploration ); précédent : 004939; suivant : 004941HLA Class II Locus and Susceptibility to Podoconiosis
Auteurs : Fasil Tekola Ayele [États-Unis, Royaume-Uni, Éthiopie] ; Adebowale Adeyemo [États-Unis] ; Chris Finan [Royaume-Uni] ; Elena Hailu [Éthiopie] ; Paul Sinnott [Royaume-Uni] ; Natalia Diaz Burlinson [Royaume-Uni] ; Abraham Aseffa [Éthiopie] ; Charles N. Rotimi [États-Unis] ; Melanie J. Newport [Royaume-Uni] ; Gail Davey [Royaume-Uni]Source :
- The New England journal of medicine [ 0028-4793 ] ; 2012.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Médecine.
English descriptors
- KwdEn :
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 noncommunicable 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.).
Affiliations:
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<series><title level="j" type="main">The New England journal of medicine</title>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Class II histocompatibility antigen</term>
<term>Elephantiasis</term>
<term>Locus</term>
<term>Lymphedema</term>
<term>Medicine</term>
<term>Podoconiosis</term>
<term>Predisposition</term>
<term>Sensitivity</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Lymphoedème</term>
<term>Antigène histocompatibilité classe II</term>
<term>Locus</term>
<term>Eléphantiasis</term>
<term>Sensibilité</term>
<term>Prédisposition</term>
<term>Médecine</term>
<term>Podoconiose</term>
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<front><div type="abstract" xml:lang="en">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<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 HLA-DQB1, HLA-DQA1, and HLA-DRB1. We confirmed these associations using family-based association testing. HLA typing showed the alleles HLA-DRB1<sup>*</sup>
0701 (odds ratio, 2.00), DQA1<sup>*</sup>
0201 (odds ratio, 1.91), and DQB1<sup>*</sup>
0202 (odds ratio, 1.79) and the HLA-DRB1<sup>*</sup>
0701-DQB1<sup>*</sup>
0202 haplotype (odds ratio, 1.92) were risk variants for podoconiosis. CONCLUSIONS Association between variants in HLA class II loci with podoconiosis (a noncommunicable 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.).</div>
</front>
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<name sortKey="Aseffa, Abraham" sort="Aseffa, Abraham" uniqKey="Aseffa A" first="Abraham" last="Aseffa">Abraham Aseffa</name>
<name sortKey="Hailu, Elena" sort="Hailu, Elena" uniqKey="Hailu E" first="Elena" last="Hailu">Elena Hailu</name>
</country>
</tree>
</affiliations>
</record>
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