title: Association between combinations of glutathione-S-transferase M1, T1 and P1 genotypes and non-alcoholic fatty liver disease.
abstract: OBJECTIVE
  Glutathione-S-transferases (GSTs) play a crucial role in antioxidant defence mechanisms, by detoxifying xenobiotics and by inactivating endogenous byproducts of oxidative stress. Functional failure, as a sequel of an altered GST genotype, may thus aggravate non-alcoholic fatty liver disease (NAFLD). This study investigated whether the GSTs genotypes could affect the risk for NAFLD.
  
  
  METHODS
  A cross-sectional case-control analysis included 253 Japanese participants in a health screening programme. The GSTM1 null, GSTT1 null and GSTP1 Ile105Val variant genotypes were determined as putative high-risk genotypes.
  
  
  RESULTS
  The incidence of NAFLD was 27.3%. The frequency of the GSTM1 null genotype was higher in NAFLD than in the control [adjusted odds ratio (OR), 2.00; 95% confidence intervals (CI), 1.01-3.95]. Moreover, any combination of two putative high-risk genotypes exhibited a higher risk for NAFLD with an adjusted OR from 3.52 (95% CI, 1.08-11.43)-4.01 (95% CI, 1.28-12.56). However, the significance for the combination of GSTM1 null and GSTT1 null genotypes only remained after Bonferroni's correction. In addition, the risk for NAFLD increased as the number of high-risk genotypes, and the OR among three high-risk genotypes carriers was 9.67 (95% CI: 1.61-58.26).
  
  
  CONCLUSIONS
  This is the first report to show the impact of the GSTs genotypes on the development of NAFLD. This finding, which should be confirmed in further studies in larger populations, may help to develop a more targeted prevention programme at an early stage for subjects with an increased risk for NAFLD.
authors.affiliation: Division of Pharmacology and Therapeutics, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Hori
authors.forename: Kentaro
authors.initials: K
authors.lastname: Oniki
authors.forename: Takehiro
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Keiji
authors.initials: K
authors.lastname: Takata
authors.forename: Shuichi
authors.initials: S
authors.lastname: Mihara
authors.forename: Toru
authors.initials: T
authors.lastname: Marubayashi
authors.forename: Kazuko
authors.initials: K
authors.lastname: Nakagawa
mesh_terms: D001837:Body Weights and Measures; D003430:Cross-Sectional Studies; D005234:Fatty Liver / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007564:Japan; D008297:Male; D016017:Odds Ratio; D014463:Ultrasonography
chemical_list: D005982:Glutathione Transferase