HLA class II locus and susceptibility to podoconiosis

Tekola Ayele, Fasil, Adeyemo, Adebowale, Finan, Chris, Hailu, Elena, Sinnott, Paul, Burlinson, Natalia Diaz, Aseffa, Abraham, Rotimi, Charles N, Newport, Melanie J and Davey, Gail (2012) HLA class II locus and susceptibility to podoconiosis. New England Journal of Medicine, 366 (13). pp. 1200-1208. ISSN 0028-4793

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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.).

Item Type: Article
Schools and Departments: Brighton and Sussex Medical School > Global Health and Infection
Subjects: R Medicine > RC Internal medicine > RC0251 Constitutional diseases (General)
Depositing User: pam Thompson
Date Deposited: 12 May 2014 15:01
Last Modified: 04 Aug 2017 14:08
URI: http://sro.sussex.ac.uk/id/eprint/48361
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