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
N1 - Funding Information:
We thank K. Tokunaga for useful advice of on HLA-DP genotyping and interpretation, and technical staff of Laboratory for Genotyping Development at RIKEN for SNP genotyping at the first and second stages of the GWAS. We are also grateful to members of Hiroshima Liver Study Group and The Rotary Club of Osaka-Midosuji District 2660 Rotary International in Japan for supporting our study. This work was conducted as a part of the BioBank Japan Project that was supported by the Ministry of Education, Culture, Sports, Sciences and Technology of the Japanese government.
PY - 2009/5
Y1 - 2009/5
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 -