Complex analysis of association of inflammation gene polymorphisms with myocardial infarction

Frequencies of the carriership of alleles and genotypes of functionally important polymorphous loci of some inflammation genes (proinflammatory cytokine genes IL-6, LTA, and TNF; anti-inflammatory cytokine gene TGFB1; and CC chemokine receptor 5 gene CCR5) were analyzed in 199 ethnic Russian patients with myocardial infarction (MI) and in a control group of 142 persons of the same ethnic descent. Complex analysis by the APSampler algorithm revealed associations of MI with the carriership of all polymorphic variants either regarded as individual risk factors (insertion-deletion polymorphism of CCR5 and SNP G252A LTA) or in combination with other alleles or genotypes. The carriership of bi-or triallelic combinations was associated with MI more reliable than the carriership of any subsets: single alleles or allele pairs. The protective triallelic combination d*CCR5 + 252G*LTA + -174C*Il-6 was found to be the most significant (p = 0.0006, OR = 0.23, CI = 0.090–0.56). Separate analysis of genetic susceptibility to MI in men and women demonstrated sexual dimorphism for the CCR5 gene.