TY - JOUR
T1 - New susceptibility and resistance HLA-DP alleles to HBV-related diseases identified by a trans-ethnic association study in Asia
AU - Nishida, Nao
AU - Sawai, Hiromi
AU - Kashiwase, Koichi
AU - Minami, Mutsuhiko
AU - Sugiyama, Masaya
AU - Seto, Wai Kay
AU - Yuen, Man Fung
AU - Posuwan, Nawarat
AU - Poovorawan, Yong
AU - Ahn, Sang Hoon
AU - Han, Kwang Hyub
AU - Matsuura, Kentaro
AU - Tanaka, Yasuhito
AU - Kurosaki, Masayuki
AU - Asahina, Yasuhiro
AU - Izumi, Namiki
AU - Kang, Jong Hon
AU - Hige, Shuhei
AU - Yamamoto, Tatsuya Ide Kazuhide
AU - Sakaida, Isao
AU - Murawaki, Yoshikazu
AU - Itoh, Yoshito
AU - Tamori, Akihiro
AU - Orito, Etsuro
AU - Hiasa, Yoichi
AU - Honda, Masao
AU - Kaneko, Shuichi
AU - Mita, Eiji
AU - Suzuki, Kazuyuki
AU - Hino, Keisuke
AU - Tanaka, Eiji
AU - Mochida, Satoshi
AU - Watanabe, Masaaki
AU - Eguchi, Yuichiro
AU - Masaki, Naohiko
AU - Murata, Kazumoto
AU - Korenaga, Masaaki
AU - Mawatari, Yoriko
AU - Ohashi, Jun
AU - Kawashima, Minae
AU - Tokunaga, Katsushi
AU - Mizokami, Masashi
N1 - Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 2014/2/10
Y1 - 2014/2/10
N2 - Previous studies have revealed the association between SNPs located on human leukocyte antigen (HLA) class II genes, including HLA-DP and HLA-DQ, and chronic hepatitis B virus (HBV) infection, mainly in Asian populations. HLA-DP alleles or haplotypes associated with chronic HBV infection or disease progression have not been fully identified in Asian populations. We performed trans-ethnic association analyses of HLA-DPA1, HLA-DPB1 alleles and haplotypes with hepatitis B virus infection and disease progression among Asian populations comprising Japanese, Korean, Hong Kong, and Thai subjects. To assess the association between HLA-DP and chronic HBV infection and disease progression, we conducted high-resolution (4-digit) HLA-DPA1 and HLA-DPB1 genotyping in a total of 3,167 samples, including HBV patients, HBV-resolved individuals and healthy controls. Trans-ethnic association analyses among Asian populations identified a new risk allele HLA-DPB1*09:01 (P = 1.36x10-6; OR = 1.97; 95% CI, 1.50-2.59) and a new protective allele DPB1*02:01 (P = 5.22x10 -6; OR = 0.68; 95% CI, 0.58-0.81) to chronic HBV infection, in addition to the previously reported alleles. Moreover, DPB1*02:01 was also associated with a decreased risk of disease progression in chronic HBV patients among Asian populations (P = 1.55x10-7; OR = 0.50; 95% CI, 0.39-0.65). Trans-ethnic association analyses identified Asian-specific associations of HLA-DP alleles and haplotypes with HBV infection or disease progression. The present findings will serve as a base for future functional studies of HLA-DP molecules in order to understand the pathogenesis of HBV infection and the development of hepatocellular carcinoma.
AB - Previous studies have revealed the association between SNPs located on human leukocyte antigen (HLA) class II genes, including HLA-DP and HLA-DQ, and chronic hepatitis B virus (HBV) infection, mainly in Asian populations. HLA-DP alleles or haplotypes associated with chronic HBV infection or disease progression have not been fully identified in Asian populations. We performed trans-ethnic association analyses of HLA-DPA1, HLA-DPB1 alleles and haplotypes with hepatitis B virus infection and disease progression among Asian populations comprising Japanese, Korean, Hong Kong, and Thai subjects. To assess the association between HLA-DP and chronic HBV infection and disease progression, we conducted high-resolution (4-digit) HLA-DPA1 and HLA-DPB1 genotyping in a total of 3,167 samples, including HBV patients, HBV-resolved individuals and healthy controls. Trans-ethnic association analyses among Asian populations identified a new risk allele HLA-DPB1*09:01 (P = 1.36x10-6; OR = 1.97; 95% CI, 1.50-2.59) and a new protective allele DPB1*02:01 (P = 5.22x10 -6; OR = 0.68; 95% CI, 0.58-0.81) to chronic HBV infection, in addition to the previously reported alleles. Moreover, DPB1*02:01 was also associated with a decreased risk of disease progression in chronic HBV patients among Asian populations (P = 1.55x10-7; OR = 0.50; 95% CI, 0.39-0.65). Trans-ethnic association analyses identified Asian-specific associations of HLA-DP alleles and haplotypes with HBV infection or disease progression. The present findings will serve as a base for future functional studies of HLA-DP molecules in order to understand the pathogenesis of HBV infection and the development of hepatocellular carcinoma.
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U2 - 10.1371/journal.pone.0086449
DO - 10.1371/journal.pone.0086449
M3 - Article
C2 - 24520320
AN - SCOPUS:84895729982
VL - 9
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 2
M1 - e86449
ER -