title: Association of VARS2-SFTA2 polymorphisms with the risk of chronic hepatitis B in a Korean population.
abstract: OBJECTIVE
  Hepatitis B virus (HBV) infection is the most serious risk factor for chronic hepatitis B (CHB), cirrhosis, and hepatocellular carcinoma. Recently, several genome-wide association studies (GWASs) identified important variants associated with the risk of CHB in Asian populations. Specifically, our previous GWAS identified the VARS2-SFTA2 gene region as one of the genetic risk loci for CHB.
  
  
  METHODS
  To further characterize this association and to isolate possible causal variants within it, we performed an additional association study by genotyping more SNPs in the vicinity of the VARS2 and SFTA2 genes. In all, 14 SNPs of VARS2-SFTA2 were analysed among a total of 3902 subjects (1046 cases and 2856 controls).
  
  
  RESULTS
  Logistic regression analysis revealed that six SNPs, including the previously reported rs2532932, were significantly associated with the risk of CHB (P = 1.7 × 10(-10) ~0.002). Further linkage disequilibrium and conditional analysis identified two variants (rs9394021 and rs2517459) as new markers of genetic risk factors for CHB rather than the reported SNP from our previous study (rs2532932). To evaluate the cumulative risk for CHB based on all known genetic factors, genetic risk score (GRS) were calculated. As anticipated, the distribution of the number of risk alleles in cases vs. controls clearly differed according to the GRS. Similarly, the odds ratios (ORs) were increased (OR = 0.32-3.97).
  
  
  CONCLUSIONS
  Our findings show that common variants in the VARS2-SFTA2 gene region are significantly associated with CHB in a Korean population, which may be useful in further understanding genetic susceptibility to CHB.
authors.affiliation: Department of Genetic Epidemiology, SNP Genetics Inc., Sogang University, Seoul, Korea.
authors.forename: Hyun Sub
authors.initials: HS
authors.lastname: Cheong
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University, Seoul, Korea.
authors.forename: Jeong-Hoon
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University, Seoul, Korea.
authors.forename: Su Jong
authors.initials: SJ
authors.lastname: Yu
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University, Seoul, Korea.
authors.forename: Jung-Hwan
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University, Seoul, Korea.
authors.forename: Hyo-Suk
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Jae Youn
authors.initials: JY
authors.lastname: Cheong
authors.affiliation: Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Cho
authors.affiliation: Department of Internal Medicine, Ulsan University Hospital, Ulsan, Korea.
authors.forename: Neung Hwa
authors.initials: NH
authors.lastname: Park
authors.affiliation: Department of Genetic Epidemiology, SNP Genetics Inc., Sogang University, Seoul, Korea.
authors.forename: Byung Lae
authors.initials: BL
authors.lastname: Park
authors.affiliation: Department of Genetic Epidemiology, SNP Genetics Inc., Sogang University, Seoul, Korea.|Department of Life Science, Sogang University, Seoul, Korea.
authors.forename: Suhg
authors.initials: S
authors.lastname: Namgoong
authors.affiliation: Department of Genetic Epidemiology, SNP Genetics Inc., Sogang University, Seoul, Korea.|Department of Life Science, Sogang University, Seoul, Korea.
authors.forename: Lyoung Hyo
authors.initials: LH
authors.lastname: Kim
authors.affiliation: Department of Genetic Epidemiology, SNP Genetics Inc., Sogang University, Seoul, Korea.|Department of Life Science, Sogang University, Seoul, Korea.
authors.forename: Hyoung Doo
authors.initials: HD
authors.lastname: Shin
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University, Seoul, Korea.
authors.forename: Yoon-Jun
authors.initials: YJ
authors.lastname: Kim
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D016001:Confidence Intervals; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D055106:Genome-Wide Association Study; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D006509:Hepatitis B / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000208:ethnology* / Q000235:genetics*; D006785:Hospitals, University; D006801:Humans; D015994:Incidence; D007723:Korea / Q000453:epidemiology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D014637:Valine-tRNA Ligase / Q000235:genetics*
chemical_list: D006680:HLA Antigens; C070977:VARS2 protein, human; D014637:Valine-tRNA Ligase
keywords: SFTA2; VARS2; chronic hepatitis B; single nucleotide polymorphism