Common variants in the HLA-DRB1-HLA-DQA1 HLA class II region are associated with susceptibility to visceral leishmaniasis.
Nat Genet
; 45(2): 208-13, 2013 Feb.
Article
in En
| MEDLINE
| ID: mdl-23291585
ABSTRACT
To identify susceptibility loci for visceral leishmaniasis, we undertook genome-wide association studies in two populations 989 cases and 1,089 controls from India and 357 cases in 308 Brazilian families (1,970 individuals). The HLA-DRB1-HLA-DQA1 locus was the only region to show strong evidence of association in both populations. Replication at this region was undertaken in a second Indian population comprising 941 cases and 990 controls, and combined analysis across the three cohorts for rs9271858 at this locus showed P(combined) = 2.76 × 10(-17) and odds ratio (OR) = 1.41, 95% confidence interval (CI) = 1.30-1.52. A conditional analysis provided evidence for multiple associations within the HLA-DRB1-HLA-DQA1 region, and a model in which risk differed between three groups of haplotypes better explained the signal and was significant in the Indian discovery and replication cohorts. In conclusion, the HLA-DRB1-HLA-DQA1 HLA class II region contributes to visceral leishmaniasis susceptibility in India and Brazil, suggesting shared genetic risk factors for visceral leishmaniasis that cross the epidemiological divides of geography and parasite species.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Genetic Predisposition to Disease
/
HLA-DQ alpha-Chains
/
HLA-DRB1 Chains
/
Leishmaniasis, Visceral
Type of study:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Humans
Country/Region as subject:
America do sul
/
Asia
/
Brasil
Language:
En
Journal:
Nat Genet
Journal subject:
GENETICA MEDICA
Year:
2013
Document type:
Article