A genome-wide association study identifies variants in the HLA-DP locus associated with chronic hepatitis B in Asians.
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.
Human Genome Center, Institute of Medical Science, the University of Tokyo, Japan.
Yoichiro
Y
Kamatani
Sukanya
S
Wattanapokayakit
Hidenori
H
Ochi
Takahisa
T
Kawaguchi
Atsushi
A
Takahashi
Naoya
N
Hosono
Michiaki
M
Kubo
Tatsuhiko
T
Tsunoda
Naoyuki
N
Kamatani
Hiromitsu
H
Kumada
Aekkachai
A
Puseenam
Thanyachai
T
Sura
Yataro
Y
Daigo
Kazuaki
K
Chayama
Wasun
W
Chantratita
Yusuke
Y
Nakamura
Koichi
K
Matsuda
D044466:Asian People / Q000235:genetics*; D015331:Cohort Studies; D005828:Genetics, Population; D015894:Genome, Human; D055106:Genome-Wide Association Study; D005838:Genotype; D006682:HLA-DP Antigens / Q000235:genetics*; D059867:HLA-DP alpha-Chains; D059868:HLA-DP beta-Chains; D006239:Haplotypes; D019694:Hepatitis B, Chronic / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide
D006682:HLA-DP Antigens; D059867:HLA-DP alpha-Chains; D059868:HLA-DP beta-Chains; C071172:HLA-DPA1 antigen; C071170:HLA-DPB1 antigen