Additive effects of the chemokine receptor 2, vitamin D receptor, interleukin-6 polymorphisms and cardiovascular risk factors on the prevalence of myocardial infarction in patients below 65 years

Background: Cardiovascular risk factors (GRF) have been associated with myocardial infarction (MI), while the role of genetic risk factors (GRF) remains undetermined. Methods: Cineventriculograms of 3436 were analyzed for presence of regional function impairment as sign of MI. Genotyping for genetic polymorphism (vitamin D receptor VDR BsmI, interleukin-6 IL6-174 G/C, chemokine receptor 2 CCR2 64 V/I) was performed. CRF were assessed (hypertension, hypercholesterolemia, smoking, and diabetes mellitus). Results: In patients < 65 years (n = 1946) genotypes (VDR BB, IL6 GC/CC, CCR2 VI/II, defined as GRF) were significantly associated with the presence of MI (BB: OR 1.38, 95%Cl 1.07-1.79, p =0.016 GC/CC: 1.28, 95%Cl 1.03-1.60, p=0.028 VI/II: 1.49, 95%Cl 1.17-1.88, p=0.001). Combining four CRF (14% vs. 21% vs. 27% vs. 31% vs. 38%, p < 0.0001) and three GRF (21% vs. 25% vs. 32% vs. 44%, p < 0.0001) revealed additive effects on the prevalence of MI. The more combined CRF and GRF were present (from 0 to 7) the higher was theprevalence of MI (11% vs. 12% vs. 21% vs. 27% vs. 30% vs. 34% vs. 59%, p < 0.0001). Age was notassociated with MI. In patients >= 65 years (n = 1490) the combination of CRF was only weakly associated with MI, while GRF were not. In these patients age was a predictor of MI. Conclusion: Certain GRF might have additive but small effects on the disposition for MI before the age of 65. In older patients the tested GRF had no effect, possibly indicating a mechanism of aging rather than a purely genetic determined entity. Given the small effect of the tested genetic polymorphisms the value of testing GRF remains uncertain. (c) 2005 Elsevier Ireland Ltd. All rights reserved.