Ayele, Fasil Tekola, Adeyemo, Adebowale, Finan, Christopher, Hailu, Elena, Sinnott, Paul, Diaz Burlington, Natalia, Aseffa, Aseffa, Rotimi, Charles N., Newport, Melanie J. and Davey, Gail (2012) The HLA class II locus confers susceptibility to podoconiosis in an Ethiopian population. New England Journal of Medicine, 366 (13). pp. 1200-1208. ISSN 0028-4793Full text not available from this repository.
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%).
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.
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.
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.)
|Schools and Departments:||Brighton and Sussex Medical School > Clinical Medicine|
|Depositing User:||Grecia GarciaGarcia|
|Date Deposited:||04 Apr 2012 08:37|
|Last Modified:||18 Jun 2013 15:10|