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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
HLA class II locus and susceptibility to podoconiosis
New England Journal of Medicine, Volume 366, No. 13, Year 2012
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Description
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 singlenucleotide 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.) Copyright © 2012 Massachusetts Medical Society.
Authors & Co-Authors
Tekola-Ayele, Fasil
United States, Bethesda
National Human Genome Research Institute Nhgri
United Kingdom, Brighton
Brighton and Sussex Medical School
Ethiopia, Addis Ababa
Armauer Hansen Research Institute
Adeyemo, Adebowale A.
United States, Bethesda
National Human Genome Research Institute Nhgri
Finan, Chris I.
United Kingdom, Brighton
Brighton and Sussex Medical School
Hailu, Elena
Ethiopia, Addis Ababa
Armauer Hansen Research Institute
Sinnott, Paul
United Kingdom, London
The Royal London Hospital
Burlinson, Natalia Diaz
United Kingdom, London
The Royal London Hospital
Aseffa, Abraham
Ethiopia, Addis Ababa
Armauer Hansen Research Institute
Rotimi, Charles N.
United States, Bethesda
National Human Genome Research Institute Nhgri
Newport, Melanie J.
United Kingdom, Brighton
Brighton and Sussex Medical School
Davey, G. J.G.
United Kingdom, Brighton
Brighton and Sussex Medical School
Statistics
Citations: 135
Authors: 10
Affiliations: 4
Identifiers
Doi:
10.1056/NEJMoa1108448
ISSN:
00284793
e-ISSN:
15334406
Research Areas
Genetics And Genomics
Noncommunicable Diseases
Study Design
Case-Control Study
Study Locations
Ethiopia