Accumulation of gene polymorphisms related to oxidative stress is associated with myocardial infarction in Japanese type 2 diabetic patients

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.