title: Association of Hypoxia-Inducible Factor-2 Alpha Gene Polymorphisms with the Risk of Hepatitis B Virus-Related Liver Disease in Guangxi Chinese: A Case-Control Study.
abstract: OBJECTIVE
  Hypoxia-inducible factor-2 alpha (HIF-2a) plays a major role in the progression of disease, although the role of HIF-2α gene polymorphisms in hepatitis B virus (HBV)-related diseases remains elusive. The aim of this study is to determine whether HIF-2a rs13419896 and rs6715787 single-nucleotide polymorphisms (SNPs) are associated with susceptibility to chronic hepatitis B (CHB), liver cirrhosis (LC), or hepatocellular carcinoma (HCC).
  
  
  METHODS
  A case-control study of 107 patients with CHB, 83 patients with LC, 234 patients with HCC, and 224 healthy control subjects was carried out, and the HIF-2a rs13419896 and rs6715787 SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
  
  
  RESULTS
  No significant differences were observed in the genotype or allele frequency of two HIF-2a SNPs between the cases and controls (all p>0.05). However, in subgroup analysis by gender, the HIF-2a rs13419896 GA and AA genotypes were significantly associated with a risk of CHB (odds ratio [OR] = 3.565, 95% confidence interval [CI] = 1.123-11.314, p = 0.031 and OR = 12.506, 95% CI = 1.329-117.716, p = 0.027) in females, and the A allele of rs13419896 was associated with a risk of CHB (OR = 2.624, 95% CI = 1.244-5.537, p = 0.011) and LC (OR = 2.351, 95% CI = 1.002-5.518, p = 0.050) in females. The rs6715787 CG genotype polymorphism may contribute to a reduced risk of LC in the Guangxi Zhuang Chinese population (OR = 0.152, 95% CI = 0.028-0.807, p = 0.027), as determined via subgroup analysis by ethnicity. Moreover, binary logistic regression analyses that were adjusted by drinking status indicated that the AA genotype of rs13419896 may contribute to an increased risk of LC in the non-alcohol-drinking population (OR = 3.124, 95% CI = 1.091-8.947, p = 0.034). In haplotype analysis, GG haplotype was significantly associated with a reduced risk of LC (OR = 0.601, 95% CI = 0.419-0.862, p = 0.005).
  
  
  CONCLUSIONS
  The HIF-2a rs13419896 polymorphism is associated with an increased risk of CHB and LC in the Guangxi Chinese population, especially in females and in the non-alcohol-drinking population, while the HIF-2a gene rs6715787 polymorphism is associated with a decreased risk of LC in the Guangxi Zhuang population.
authors.affiliation: Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.|Department of Clinical Laboratory, Longtan Hospital of Guangxi Zhuang Autonomous Region, Liuzhou, Guangxi, China.
authors.forename: Liling
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Infectious Disease, Longtan Hospital of Guangxi Zhuang Autonomous Region, Liuzhou, Guangxi, China.
authors.forename: Cunxu
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
authors.forename: Yanqiong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
authors.forename: Jiangyang
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Tang
authors.affiliation: Department of Clinical Laboratory, Third Affiliated Hospital of Guangxi University of Chinese Medicine, Liuzhou, Guangxi, China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Qin
authors.affiliation: Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Li
mesh_terms: D000328:Adult; D000428:Alcohol Drinking; D000483:Alleles; D044466:Asian People; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000208:ethnology / Q000235:genetics; D016022:Case-Control Studies; D002681:China; D005260:Female; D005355:Fibrosis / Q000208:ethnology / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006515:Hepatitis B virus; D019694:Hepatitis B, Chronic / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D008107:Liver Diseases / Q000208:ethnology / Q000235:genetics*; D008113:Liver Neoplasms / Q000208:ethnology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D000099162:Endothelial PAS Domain-Containing Protein 1