Nishida Nao, Sawai Hiromi, Kashiwase Koichi, Minami Mutsuhiko, Sugiyama Masaya, Seto Wai-Kay, Yuen Man-Fung, Posuwan Nawarat, Poovorawan Yong, Ahn Sang Hoon, Han Kwang-Hyub, Matsuura Kentaro, Tanaka Yasuhito, Kurosaki Masayuki, Asahina Yasuhiro, Izumi Namiki, Kang Jong-Hon, Hige Shuhei, Ide Tatsuya, Yamamoto Kazuhide, Sakaida Isao, Murawaki Yoshikazu, Itoh Yoshito, Tamori Akihiro, Orito Etsuro, Hiasa Yoichi, Honda Masao, Kaneko Shuichi, Mita Eiji, Suzuki Kazuyuki, Hino Keisuke, Tanaka Eiji, Mochida Satoshi, Watanabe Masaaki, Eguchi Yuichiro, Masaki Naohiko, Murata Kazumoto, Korenaga Masaaki, Mawatari Yoriko, Ohashi Jun, Kawashima Minae, Tokunaga Katsushi, Mizokami Masashi
The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan ; Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
PLoS One. 2014 Feb 10;9(2):e86449. doi: 10.1371/journal.pone.0086449. eCollection 2014.
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-DPB109 ∶ 01 (P = 1.36 × 10(-6); OR= 1.97; 95% CI, 1.50-2.59) and a new protective allele DPB102 ∶ 01 (P = 5.22 × 10(-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 = 1.55 × 10(-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.
先前的研究揭示了位于人类白细胞抗原（HLA）II类基因（包括HLA-DP和HLA-DQ）上的单核苷酸多态性（SNP）与慢性乙型肝炎病毒（HBV）感染之间的关联，主要是在亚洲人群中。在亚洲人群中，与慢性HBV感染或疾病进展相关的HLA-DP等位基因或单倍型尚未完全明确。我们对包括日本、韩国、中国香港和泰国受试者在内的亚洲人群进行了HLA-DPA1、HLA-DPB1等位基因和单倍型与乙型肝炎病毒感染及疾病进展的跨种族关联分析。为了评估HLA-DP与慢性HBV感染及疾病进展之间的关联，我们对总共3167份样本进行了高分辨率（4位数字）的HLA-DPA1和HLA-DPB1基因分型，这些样本包括HBV患者、HBV康复个体和健康对照。亚洲人群之间的跨种族关联分析确定了一个新的风险等位基因HLA-DPB109∶01（P = 1.36×10⁻⁶；OR = 1.97；95%CI，1.50 - 2.59）和一个新的保护性等位基因DPB102∶01（P = 5.22×10⁻⁶；OR = 0.68；95%CI，0.58 - 0.81）与慢性HBV感染相关，此外还有先前报道的等位基因。此外，DPB1*02∶01在亚洲人群的慢性HBV患者中也与疾病进展风险降低相关（P = 1.55×10⁻⁷；OR = 0.50；95%CI，0.39 - 0.65）。跨种族关联分析确定了HLA-DP等位基因和单倍型与HBV感染或疾病进展的亚洲特异性关联。本研究结果将为未来HLA-DP分子的功能研究奠定基础，以便了解HBV感染的发病机制和肝细胞癌的发展。
