TY - JOUR
T1 - A genome-wide association study identifies variants in the HLA-DP locus associated with chronic hepatitis B in Asians
AU - Kamatani, Yoichiro
AU - Wattanapokayakit, Sukanya
AU - Ochi, Hidenori
AU - Kawaguchi, Takahisa
AU - Takahashi, Atsushi
AU - Hosono, Naoya
AU - Kubo, Michiaki
AU - Tsunoda, Tatsuhiko
AU - Kamatani, Naoyuki
AU - Kumada, Hiromitsu
AU - Puseenam, Aekkachai
AU - Sura, Thanyachai
AU - Daigo, Yataro
AU - Chayama, Kazuaki
AU - Chantratita, Wasun
AU - Nakamura, Yusuke
AU - Matsuda, Koichi
PY - 2009/5/1
Y1 - 2009/5/1
N2 - 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 individuals1. 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 × 10-39 and 2.31 × 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.
AB - 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 individuals1. 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 × 10-39 and 2.31 × 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.
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U2 - 10.1038/ng.348
DO - 10.1038/ng.348
M3 - Article
C2 - 19349983
AN - SCOPUS:67349160018
VL - 41
SP - 591
EP - 595
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 5
ER -