title: A candidate gene study for the association of host single nucleotide polymorphisms with liver cirrhosis risk in chinese hepatitis B patients.
abstract: OBJECTIVE
  Recently, genetic association studies have linked a number of single nucleotide polymorphisms (SNPs) with liver fibrosis risk of hepatitis C. The present study was designed to validate the association of emerging SNPs with development of liver cirrhosis and chronicity in a Chinese population infected with hepatitis B virus (HBV).
  
  
  METHODS
  714 Chinese subjects with persistent HBV infection (429 with evident liver cirrhosis and 285 without cirrhosis clinically or pathologically) and 280 subjects with spontaneous HBV clearance were studied. Six SNPs in five candidate genes were detected with the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) method. The distribution of each polymorphism was compared between the age-matched cirrhotic and noncirrhotic subjects, and between subjects with persistent infection and spontaneous HBV clearance.
  
  
  RESULTS
  The rs2679757 polymorphism of antizyme inhibitor 1 (AZIN1) gene was associated with the risk of cirrhosis (odds ratio [OR] for GG+AG versus AA=1.47, 95% confidence interval [CI]=1.08-2.01, p=0.01). So was rs886277 in the transient receptor potential cation channel subfamily M, member 5 (TRPM5) gene (OR for CC versus CT+TT=1.63, 95% CI=1.20-2.22, p=0.002). The frequencies of these two SNPs were also associated with the severity of decompensated cirrhosis based on the Child-Pugh classification. Genotype frequencies of other SNPs were not different between the cirrhotic and noncirrhotic groups. No SNPs were associated with the outcome of spontaneous HBV clearance.
  
  
  CONCLUSIONS
  AZIN1 rs2679757 and TRPM5 rs886277 are associated with the risk of HBV-related liver cirrhosis in Chinese. The emerging SNPs warrant further clinical validation in other cohorts or ethnic groups, and could lead to mechanistic studies to reveal their contributions to fibrosis progression.
authors.affiliation: Division of Digestive Diseases, Department of Internal Medicine, Zhong Shan Hospital, Shanghai Medical College, Fu Dan University, Shanghai, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Peng
authors.forename: Jinsheng
authors.initials: J
authors.lastname: Guo
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.forename: Lili
authors.initials: L
authors.lastname: Liu
authors.forename: Yirong
authors.initials: Y
authors.lastname: Cao
authors.forename: Hong
authors.initials: H
authors.lastname: Shi
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Jiyao
authors.initials: J
authors.lastname: Wang
authors.forename: Scott L
authors.initials: SL
authors.lastname: Friedman
authors.forename: John J
authors.initials: JJ
authors.lastname: Sninsky
mesh_terms: D044466:Asian People; D002352:Carrier Proteins / Q000235:genetics*; D002681:China / Q000453:epidemiology; D005260:Female; D005838:Genotype; D006509:Hepatitis B / Q000150:complications / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008103:Liver Cirrhosis / Q000453:epidemiology / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D050053:TRPM Cation Channels / Q000235:genetics*
chemical_list: C484011:AZIN1 protein, human; D002352:Carrier Proteins; D050053:TRPM Cation Channels; C404409:TRPM5 protein, human