title: Accumulation of gene polymorphisms related to oxidative stress is associated with myocardial infarction in Japanese type 2 diabetic patients.
abstract: OBJECTIVE
  It is believed that oxidative stress, which is provoked in patients with diabetes, plays critical roles in the pathogenesis of myocardial infarction (MI). We simultaneously determined 5 relatively common genetic variants related to oxidative stress and evaluated the combined effect on MI.
  
  
  METHODS
  We enrolled 3819 Japanese type 2 diabetic subjects (males 60.8%, 60.6±10.0 years old) and 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. The diagnosis of the occurrence of MI was based on the clinical records, characteristic ECG changes, and the findings in coronary angiography and echocardiography.
  
  
  RESULTS
  The single association analysis revealed that there were no statistically significant associations between each polymorphism and the prevalence of MI. Interestingly, the prevalence of MI was higher with the increase of the total number of 5 concomitant unfavorable "pro-oxidant alleles" in each subject (p value for linear trend=0.018). Furthermore, a multiple logistic regression analysis showed that the number of pro-oxidant alleles was a risk factor for MI independently of conventional risk factors (odds ratio for 1-point increase in the number of pro-oxidant allele=1.16 with 95% CI 1.01-1.34, p=0.034).
  
  
  CONCLUSIONS
  Accumulation of gene polymorphisms related to oxidative stress is likely associated with the prevalence of MI in type 2 diabetic patients, suggesting that the combined information about these variants is useful to assess the risk of MI.
authors.affiliation: Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan. katakami@medone.med.osaka-u.ac.jp
authors.forename: Naoto
authors.initials: N
authors.lastname: Katakami
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kaneto
authors.forename: Taka-aki
authors.initials: TA
authors.lastname: Matsuoka
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Takahara
authors.forename: Kenichi
authors.initials: K
authors.lastname: Imamura
authors.forename: Fukashi
authors.initials: F
authors.lastname: Ishibashi
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Kanda
authors.forename: Koichi
authors.initials: K
authors.lastname: Kawai
authors.forename: Takeshi
authors.initials: T
authors.lastname: Osonoi
authors.forename: Atsunori
authors.initials: A
authors.lastname: Kashiwagi
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Kawamori
authors.forename: Munehide
authors.initials: M
authors.lastname: Matsuhisa
authors.forename: Iichiro
authors.initials: I
authors.lastname: Shimomura
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Yamasaki
mesh_terms: D000368:Aged; D050197:Atherosclerosis; D048909:Diabetes Complications / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications* / Q000235:genetics*; D016877:Oxidants / Q000737:chemistry; D018384:Oxidative Stress; D011110:Polymorphism, Genetic; D012306:Risk
chemical_list: D016877:Oxidants