A genome-wide association study identifies variants in the HLA-DP locus associated with chronic hepatitis B in Asians.

Nat Genet 2009 May 6;41(5):591-5. Epub 2009 Apr 6.

Human Genome Center, Institute of Medical Science, the University of Tokyo, Japan.

Chronic hepatitis B is a serious infectious liver disease that often progresses to liver cirrhosis and hepatocellular carcinoma; however, clinical outcomes after viral exposure vary enormously among individuals. Through a two-stage genome-wide association study using 786 Japanese chronic hepatitis B cases and 2,201 controls, we identified a significant association of chronic hepatitis B with 11 SNPs in a region including HLA-DPA1 and HLA-DPB1. We validated these associations by genotyping two SNPs from the region in three additional Japanese and Thai cohorts consisting of 1,300 cases and 2,100 controls (combined P = 6.34 x 10(-39) and 2.31 x 10(-38), OR = 0.57 and 0.56, respectively). Subsequent analyses revealed risk haplotypes (HLA-DPA1(*)0202-DPB1(*)0501 and HLA-DPA1(*)0202-DPB1(*)0301, OR = 1.45 and 2.31, respectively) and protective haplotypes (HLA-DPA1(*)0103-DPB1(*)0402 and HLA-DPA1(*)0103-DPB1(*)0401, OR = 0.52 and 0.57, respectively). Our findings show that genetic variants in the HLA-DP locus are strongly associated with risk of persistent infection with hepatitis B virus.

Download full-text PDF

Source
http://dx.doi.org/10.1038/ng.348DOI Listing
May 2009

Publication Analysis

Top Keywords

chronic hepatitis
16
hla-dp locus
8
snps region
8
variants hla-dp
8
association study
8
genome-wide association
8
locus associated
8
hepatitis
5
231 protective
4
protective haplotypes
4
region including
4
hla-dpa1 hla-dpb1
4
hla-dpa1*0202-dpb1*0301 145
4
associations genotyping
4
validated associations
4
145 231
4
hla-dpb1 validated
4
including hla-dpa1
4
identified association
4
hepatitis cases
4

Similar Publications