title: A genetic variant of the NTCP gene is associated with HBV infection status in a Chinese population.
abstract: BACKGROUND
  To investigate whether genetic variants of the HBV receptor gene NTCP are associated with HBV infection in the Han Chinese population.
  
  
  METHODS
  We sequenced the entire 23 kb NTCP gene from 111 HBeAg-positive HBsAg carriers (PSE group), 110 HBeAg-negative HBsAg carriers (PS group), and 110 control subjects. Then, we performed association analyses of suggestively significant SNPs with HBV infection in 1075 controls, 1936 PSs and 639 PSEs.
  
  
  RESULTS
  In total, 109 rare variants (74 novel) and 38 single nucleotide polymorphisms (SNPs, one novel) were screened. Of the seven non-synonymous rare variants, six were singletons and one was a double hit. All three damaging rare singletons presented exclusively in the PSE group. Of the five SNPs validated in all 3650 subjects, the T allele of rs4646287 was significantly decreased (p = 0.002) in the PS group (10.1%) and PSE group (8.1%) compared to the controls (10.9%) and was decreased to 7.4% in the PSE hepatocellular carcinoma (HCC) subgroup. Additionally, rs4646287-T was associated with a 0.68-fold (95% CI = 0.51-0.89, p = 0.006) decreased risk of PSE compared with the controls. The NTCP mRNA level was lower in HCC tissues in "CT + TT" carriers than in "CC" carriers.
  
  
  CONCLUSIONS
  We found a genetic variant (rs4646287) located in intron 1 of NTCP that may be associated with increased risk of HBV infection in Han Chinese.
authors.affiliation: Epidemiology unit of MOE Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences and Institutes of Biomedical Sciences, Fudan University, 220 Handan Rd., Shanghai, 200433, China.|China Medical City Institute of Health Sciences, 1 Yaocheng Road, Taizhou, Jiangsu, 225300, China.
authors.forename: Jingmin
authors.initials: J
authors.lastname: Yang
authors.affiliation: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China.|Department of Health Statistics, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Epidemiology unit of MOE Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences and Institutes of Biomedical Sciences, Fudan University, 220 Handan Rd., Shanghai, 200433, China.|China Medical City Institute of Health Sciences, 1 Yaocheng Road, Taizhou, Jiangsu, 225300, China.
authors.forename: Mingying
authors.initials: M
authors.lastname: Xia
authors.affiliation: Epidemiology unit of MOE Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences and Institutes of Biomedical Sciences, Fudan University, 220 Handan Rd., Shanghai, 200433, China.|China Medical City Institute of Health Sciences, 1 Yaocheng Road, Taizhou, Jiangsu, 225300, China.
authors.forename: Lianghui
authors.initials: L
authors.lastname: Wang
authors.affiliation: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China.|National Innovation Alliance for Hepatitis & Liver Cancer, Shanghai, 200438, China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Epidemiology unit of MOE Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences and Institutes of Biomedical Sciences, Fudan University, 220 Handan Rd., Shanghai, 200433, China.|China Medical City Institute of Health Sciences, 1 Yaocheng Road, Taizhou, Jiangsu, 225300, China.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Epidemiology unit of MOE Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences and Institutes of Biomedical Sciences, Fudan University, 220 Handan Rd., Shanghai, 200433, China.|China Medical City Institute of Health Sciences, 1 Yaocheng Road, Taizhou, Jiangsu, 225300, China.
authors.forename: Yueming
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China.|Department of Health Statistics, Second Military Medical University, Shanghai, 200433, China.|National Innovation Alliance for Hepatitis & Liver Cancer, Shanghai, 200438, China.
authors.forename: Hongyang
authors.initials: H
authors.lastname: Wang
authors.affiliation: Epidemiology unit of MOE Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences and Institutes of Biomedical Sciences, Fudan University, 220 Handan Rd., Shanghai, 200433, China. jiqian05@gmail.com.|China Medical City Institute of Health Sciences, 1 Yaocheng Road, Taizhou, Jiangsu, 225300, China. jiqian05@gmail.com.|Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, 200032, China. jiqian05@gmail.com.|Department of Oncology, Fudan University Shanghai Medical College, Shanghai, 200032, China. jiqian05@gmail.com.
authors.forename: Ji
authors.initials: J
authors.lastname: Qian
authors.affiliation: Epidemiology unit of MOE Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences and Institutes of Biomedical Sciences, Fudan University, 220 Handan Rd., Shanghai, 200433, China. lijin.fudan@gmail.com.|China Medical City Institute of Health Sciences, 1 Yaocheng Road, Taizhou, Jiangsu, 225300, China. lijin.fudan@gmail.com.
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.affiliation: Epidemiology unit of MOE Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences and Institutes of Biomedical Sciences, Fudan University, 220 Handan Rd., Shanghai, 200433, China. xiaofengwang71@163.com.|China Medical City Institute of Health Sciences, 1 Yaocheng Road, Taizhou, Jiangsu, 225300, China. xiaofengwang71@163.com.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Wang
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology / Q000821:virology; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006513:Hepatitis B e Antigens / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics / Q000472:pathogenicity; D019694:Hepatitis B, Chronic / Q000235:genetics* / Q000821:virology; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D029363:Organic Anion Transporters, Sodium-Dependent / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D027981:Symporters / Q000235:genetics*
chemical_list: D006513:Hepatitis B e Antigens; D029363:Organic Anion Transporters, Sodium-Dependent; D027981:Symporters; C071908:sodium-bile acid cotransporter
keywords: Association; Genetic variant; HBV infection status; HBV-receptor; NTCP; rs4646287