Study Suggests Genetic Factors May Help Explain High Rates of Hepatitis B among Asians

By Liz Highleyman

Hepatitis B virus (HBV) is endemic throughout much of Asia; in other parts of the world, rates are much higher among people of Asian/Pacific Islander descent. Asians are more likely to be infected with HBV at birth, and people who contract the virus at a young age are less likely to experience spontaneous clearance. This heightened vulnerability may be attributable to genetic factors, according to a study published in the May 2009 issue of Nature Genetics.

Yoichiro Kamatani and colleagues from Japan and Thailand performed a 2-stage, genome-wide association study that included 786 Japanese chronic hepatitis B patients and 2201 control subjects without hepatitis B.

The investigators identified a significant association between chronic HBV infection and the presence of 11 single nucleotide polymorphisms (SNPs), or specific genetic variations, in a region including human leukocyte antigens HLA-DPA1 and HLA-DPB1. The HLA system, or major histocompatibility complex, refers to a set of genes that regulate immune function.

The researchers were then able to validate these associations by genotyping 2 SNPs from the region in 3 additional Japanese and Thai cohorts consisting of 1300 people with chronic hepatitis B and 2100 uninfected control subjects.

Subsequent analyses revealed 2 haplotypes associated with increased risk of chronic hepatitis B:

HLA-DPA1(*)0202-DPB1(*)0501 -- odds ratio (OR) 1.45;

HLA-DPA1(*)0202-DPB1(*)0301 -- OR 2.31.

They also identified 2 apparently protective haplotypes:

HLA-DPA1(*)0103-DPB1(*)0402 -- OR 0.52;

HLA-DPA1(*)0103-DPB1(*)0401 -- OR 0.57.

In conclusion, the study authors wrote, "Our findings show that genetic variants in the HLA-DP locus are strongly associated with risk of persistent infection with hepatitis B virus."

Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science and Department of Medical Genome Sciences, Graduate School of Frontier Sciences, University of Tokyo, Tokyo, Japan; Medical Genetic Section, National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand; Center for Genomic Medicine, RIKEN, Kanagawa, Japan; Department of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan; Department of Hepatology, Toranomon Hospital, Tokyo, Japan; Department of Medicine and Virology and Molecular Microbiology Unit, Department of Pathology, Ramathidi Hospital, Mahidol University, Bangkok, Thailand.

5/22/09

Reference
Y Kamatani, S Wattanapokayakit, H Ochi, and others. A genome-wide association study identifies variants in the HLA-DP locus associated with chronic hepatitis B in Asians. Nature Genetics 41(5): 591-595. May 2009. (Abstract).