title: Genetic association of glutathione peroxidase-1 with coronary artery calcification in type 2 diabetes: a case control study with multi-slice computed tomography.
abstract: BACKGROUND
  Although oxidative stress by accumulation of reactive oxygen species (ROS) in diabetes has become evident, it remains unclear what genes, involved in redox balance, would determine susceptibility for development of atherosclerosis in diabetes. This study evaluated the effect of genetic polymorphism of enzymes producing or responsible for reducing ROS on coronary artery calcification in type 2 diabetes (T2D).
  
  
  METHODS
  An index for coronary-arteriosclerosis, coronary artery calcium score (CACS) was evaluated in 91 T2D patients using a multi-slice computed tomography. Patients were genotyped for ROS-scavenging enzymes, Glutathione peroxidase-1 (GPx-1), Catalase, Mn-SOD, Cu/Zn-SOD, as well as SNPs of NADPH oxidase as ROS-promoting elements, genes related to onset of T2D (CAPN10, ADRB3, PPAR gamma, FATP4). Age, blood pressure, BMI, HbA1c, lipid and duration of diabetes were evaluated for a multivariate regression analysis.
  
  
  RESULTS
  CACS with Pro/Leu genotype of the GPx-1 gene was significantly higher than in those with Pro/Pro (744 +/- 1,291 vs. 245 +/- 399, respectively, p = 0.006). In addition, genotype frequency of Pro/Leu in those with CACS >or= 1000 was significantly higher than in those with CACS < 1000 (45.5% vs. 18.8%; OR = 3.61, CI = 0.97-13.42; p = 0.045) when tested for deviation from Hardy-Weinberg's equilibrium. Multivariate regression analyses revealed that CACS significantly correlated with GPx-1 genotypes and age.
  
  
  CONCLUSIONS
  The presence of Pro197Leu substitution of the GPx-1 gene may play a crucial role in determining genetic susceptibility to coronary-arteriosclerosis in T2D. The mechanism may be associated with a decreased ability to scavenge ROS with the variant GPx-1.
authors.affiliation: Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan. mnemoto@kje.biglobe.ne.jp
authors.forename: Masami
authors.initials: M
authors.lastname: Nemoto
authors.forename: Rimei
authors.initials: R
authors.lastname: Nishimura
authors.forename: Takashi
authors.initials: T
authors.lastname: Sasaki
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Hiki
authors.forename: Yumi
authors.initials: Y
authors.lastname: Miyashita
authors.forename: Makiko
authors.initials: M
authors.lastname: Nishioka
authors.forename: Kei
authors.initials: K
authors.lastname: Fujimoto
authors.forename: Toru
authors.initials: T
authors.lastname: Sakuma
authors.forename: Toya
authors.initials: T
authors.lastname: Ohashi
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Fukuda
authors.forename: Yoshikatsu
authors.initials: Y
authors.lastname: Eto
authors.forename: Naoko
authors.initials: N
authors.lastname: Tajima
mesh_terms: D019943:Amino Acid Substitution; D002114:Calcinosis / Q000000981:diagnostic imaging / Q000201:enzymology / Q000235:genetics*; D016022:Case-Control Studies; D003327:Coronary Disease / Q000000981:diagnostic imaging / Q000201:enzymology / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000235:genetics*; D003925:Diabetic Angiopathies / Q000000981:diagnostic imaging / Q000201:enzymology / Q000235:genetics*; D005260:Female; D005838:Genotype; D005979:Glutathione Peroxidase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D014057:Tomography, X-Ray Computed; D000094765:Glutathione Peroxidase GPX1