Wang Peng, Mo Ruidong, Lai Rongtao, Xu Yumin, Lu Jie, Zhao Gangde, Liu Yuhan, Cao Zhujun, Wang Xiaolin, Li Ziqiang, Lin Lanyi, Zhou Huijuan, Cai Wei, Wang Hui, Bao Shisan, Xiang Xiaogang, Xie Qing
Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Translational Lab of Liver Diseases, Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Oncotarget. 2017 Oct 31;8(62):105407-105424. doi: 10.18632/oncotarget.22211. eCollection 2017 Dec 1.
Sodium taurocholate cotransporting polypeptide (NTCP), encoded by gene SLC10A1, is a receptor for hepatitis B virus (HBV). The aim of the current study was to investigate the role of NTCP polymorphisms in HBV susceptibility, cirrhosis and hepatocarcinogenesis. A total 1221 cases [including 866 chronic hepatitis B (CHB), 238 liver cirrhosis (LC), 117 hepatocellular carcinoma (HCC) patients] and 1232 healthy controls (HCs) were recruited, and 6 single nucleotide polymorphisms (SNPs) were genotyped. Meta-analysis was executed among 14591 CHBs and 12396 HCs to determine the association between NTCP polymorphisms and HBV infection, cirrhosis or hepatocarcinogenesis. The frequency of rs2296651-GA was inversely correlated with CHB, LC or HCC patients [adjusted OR(95%CI)=0.16(0.11-0.23), <0.001; 0.34(0.21-0.55), =0.001; or 0.46(0.25-0.83), =0.008], respectively, compared with HCs. Meta-analysis also showed that NTCP rs2296651-GA was inversely associated with HBV infection [OR(95%CI)=0.532(0.287-0.986), =0.028, codominant] or HBV-related HCC [OR(95%CI)=0.701(0.564-0.872), =0.001, recessive]. Furthermore, the frequency of rs943277-GA was positively correlated with HBV infection [adjusted OR(95%CI)=2.42(1.05-5.54), =0.032, codominant]. Our data suggest that NTCP mutants contribute to the susceptibility of HBV infection or HBV-related HCC.
由基因SLC10A1编码的牛磺胆酸钠共转运多肽（NTCP）是乙肝病毒（HBV）的一种受体。本研究旨在探讨NTCP基因多态性在HBV易感性、肝硬化及肝癌发生中的作用。共纳入1221例患者[包括866例慢性乙型肝炎（CHB）、238例肝硬化（LC）、117例肝细胞癌（HCC）患者]和1232例健康对照（HC），对6个单核苷酸多态性（SNP）进行基因分型。对14591例CHB患者和12396例HC进行荟萃分析，以确定NTCP基因多态性与HBV感染、肝硬化或肝癌发生之间的关联。与HC相比，rs2296651 - GA的频率与CHB、LC或HCC患者呈负相关[校正OR（95%CI）=0.16（0.11 - 0.23），<0.001；0.34（0.21 - 0.55），=0.001；或0.46（0.25 - 0.83），=0.008]。荟萃分析还显示，NTCP rs2296651 - GA与HBV感染呈负相关[OR（95%CI）=0.532（0.287 - 0.986），=0.028，共显性]或与HBV相关的HCC呈负相关[OR（95%CI）=0.701（0.564 - 0.872），=0.001，隐性]。此外，rs943277 - GA的频率与HBV感染呈正相关[校正OR（95%CI）=2.42（1.05 - 5.54），=0.032，共显性]。我们的数据表明，NTCP突变体与HBV感染或HBV相关的HCC易感性有关。
