Genetic variations of NTCP are associated with susceptibility to HBV infection and related hepatocellular carcinoma
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Peng Wang1,2,*, Ruidong Mo1,2,*, Rongtao Lai1,2,*, Yumin Xu1,2, Jie Lu2, Gangde Zhao1,2, Yuhan Liu1,2, Zhujun Cao1,2, Xiaolin Wang1,2, Ziqiang Li1,2, Lanyi Lin1, Huijuan Zhou1, Wei Cai1, Hui Wang1, Shisan Bao1,3, Xiaogang Xiang1,2 and Qing Xie1,2
1Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
2Translational Lab of Liver Diseases, Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
3Discipline of Pathology, School of Medical Sciences and Bosch Institute, The University of Sydney, New South Wales 2006, Australia
*These authors have contributed equally to this work
Qing Xie, email: [email protected]
Xiaogang Xiang, email: [email protected]
Keywords: Na+ taurocholate cotransporting polypeptide; association study; HBV; HCC; meta-analysis
Received: July 19, 2017 Accepted: September 21, 2017 Published: October 31, 2017
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), p<0.001; 0.34(0.21-0.55), p=0.001; or 0.46(0.25-0.83), p=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), p=0.028, codominant] or HBV-related HCC [OR(95%CI)=0.701(0.564-0.872), p=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), p=0.032, codominant]. Our data suggest that NTCP mutants contribute to the susceptibility of HBV infection or HBV-related HCC.
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