The G972R Polymorphism in the Insulin Receptor Substrate (IRS)-1 Gene does not Correlate with Angiographic Presence of Significant Coronary Artery Disease

Journal of Clinical and Basic Cardiology 2005; 8 (1-4): 61-64

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Keywords: Diabetes mellitus,  Insulinresistenz,  IRS-1-Gen,  Kardiologie,  Koronarangiographie,  koronare Arterienerkrankung,  coronary angiography,  coronary artery disease,  diabetes mellitus type 2,  insulin resistance,  IRS-1 gene

A base change at codon 972 of the insulin receptor substrate-1 (IRS-1) gene resulting in an arginine for glycine substitution has been found to be associated with insulin resistance and predisposition to non-insulin dependent diabetes mellitus. Some data exist about the possible contribution of the G972R mutation to development of coronary artery disease (CAD). We conducted a case-control study in order to test the frequency and possible association of this common mutation with the presence of CAD in 436 consecutive Austrian subjects undergoing coronary angiography. Genotypes of IRS-1 polymorphism were determined in 215 patients with significant (stenosis > 50 %) CAD and in 221 controls free of coronary atherosclerosis. The frequency of G972R mutation carriers was identical in the patient and control group (12.1 % vs. 12.2 %, p = n.s.) except for a higher prevalence in a small subgroup of male subjects with diabetes. Consequently, regression analysis revealed no association between this common mutation and CAD independent of typical risk factors in both gender. The group of CAD contained 44 (20.5 %) patients with diabetes, whereas only 19 (8.6 %) diabetics were found in the control arm (p <0.001). Among 63 diabetic individuals of the total study population the frequency of the IRS-1 mutation was almost 2-times higher than among non-diabetics (20.6 % vs. 10.7 %, p < 0.003). Male mutation carriers showed significantly higher values of fasting insulin, female mutation carriers of triglycerides and LDL cholesterol. Data of the present study do not suggest that the G972R mutation is a genetic marker for the presence of significant CAD in patients stratified by coronary angiography.