title: Accumulation of oxidative stress-related gene polymorphisms and the risk of coronary heart disease events in patients with type 2 diabetes--an 8-year prospective study.
abstract: OBJECTIVE
  Oxidative stress, which is provoked in patients with diabetes, plays critical roles in the pathogenesis of coronary heart disease (CHD). We simultaneously determined 5 relatively common genetic variants related to oxidative stress and evaluated the combined effect on CHD.
  
  
  METHODS
  We enrolled 1977 Japanese type 2 diabetic subjects without history of CVD (males 66.1%, 59.5 ± 10.0 years old), determined their genotypes regarding glutamate-cysteine ligase modifier subunit (GCLM) C-588T, manganese superoxide dismutase (SOD2) Val16Ala, endothelial nitric oxide synthase (NOS3) G894T, NAD(P)H oxidase p22phox (CYBA) C242T, and myeloperoxidase (MPO) G-463A polymorphisms, and prospectively evaluated the association between these polymorphisms and CHD events.
  
  
  RESULTS
  The median follow-up period was 7.5 years and there were 85 new CHD events. The single association analysis revealed that there were no statistically significant associations between each polymorphism and the prevalence of CHD. Interestingly, the risk of CHD event was higher with the increase of the total number of 10 concomitant unfavorable "pro-oxidant alleles" in each subject (p for trend = 0.018, log-rank test). Especially, the carriers of ≥8 pro-oxidant alleles had a significantly increased risk as compared to the carriers of <8 pro-oxidant alleles, whether the other clinical variables were adjusted (HR 2.92 with 95%CI 1.50-5.67, p = 0.002) or not (HR 2.89 with 95%CI 1.49-5.59, p = 0.002)..
  
  
  CONCLUSIONS
  Accumulation of gene polymorphisms related to oxidative stress is likely associated with the development of CHD in patients with type 2 diabetes, suggesting that the combined information about these variants is useful to assess the risk of CHD.
authors.affiliation: Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Japan; Department of Metabolism and Atherosclerosis, Osaka University Graduate School of Medicine, Japan. Electronic address: katakami@endmet.med.osaka-u.ac.jp.
authors.forename: Naoto
authors.initials: N
authors.lastname: Katakami
authors.affiliation: Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kaneto
authors.affiliation: Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Japan.
authors.forename: Taka-Aki
authors.initials: TA
authors.lastname: Matsuoka
authors.affiliation: Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Japan.
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Takahara
authors.affiliation: Naka Memorial Clinic, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Osonoi
authors.affiliation: Naka Memorial Clinic, Japan.
authors.forename: Miyoko
authors.initials: M
authors.lastname: Saitou
authors.affiliation: Kawai Clinic, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Kawai
authors.affiliation: Ishibashi Clinic, Japan.
authors.forename: Fukashi
authors.initials: F
authors.lastname: Ishibashi
authors.affiliation: Department of Medicine, Shiga University of Medical Science, Japan.
authors.forename: Atsunori
authors.initials: A
authors.lastname: Kashiwagi
authors.affiliation: Sportology Center, Juntendo University School of Medicine, Japan.
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Kawamori
authors.affiliation: Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Japan.
authors.forename: Iichiro
authors.initials: I
authors.lastname: Shimomura
authors.affiliation: Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Japan.
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Yamasaki
mesh_terms: D000368:Aged; D044466:Asian People; D003327:Coronary Disease / Q000209:etiology / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005721:Glutamate-Cysteine Ligase / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D019255:NADPH Oxidases / Q000235:genetics; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics*; D009195:Peroxidase / Q000235:genetics; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012307:Risk Factors; D013482:Superoxide Dismutase / Q000235:genetics; D000099156:Superoxide Dismutase 2
chemical_list: D005721:Glutamate-Cysteine Ligase; D019255:NADPH Oxidases; D052250:Nitric Oxide Synthase Type III; D009195:Peroxidase; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C496314:NOS3 protein, human; C086986:CYBA protein, human; C546365:GCLM protein, human
keywords: Atherosclerosis; Coronary heart disease; Diabetes; Oxidative stress; Polymorphism