Synergic predisposing effect of G894T (eNOS), 4G/5G (PAI) and T1131C (APOA5) polymorphisms to myocardial infarction

Abstract Background Association studies around the world have investigated the influence of one Single Nucleotide Polymorphism (SNP) or many SNPs in one gene, which usually resulted in limited and inconclusive information that is difficult to replicate in case-control studies across different populations having different genetic background. Objective In this study, we attempt to analyze the effect of gene-gene interaction on MI' risk of occurrence, by studying the combinations of G894T eNOS-4G/5G PAI, G894T eNOS-T1131C APOA5 and 4G/5G PAI-T1131C APOA5, and evaluating the dependence or non-dependence of their single effects on MI risk. Material and methods 118 patients Vs 184 apparently healthy subjects were recruited, and DNA extraction was performed using sating-out standard method. Genotypes for the studied polymorphisms were determined by PCR-RFLP. Results Our results suggest that the eNOS and APOA5 genes might be dependently associated with MI' risk of occurrence, as the P values of the associated genotype-combinations were lower than those obtained by the analysis of each gene separately. The associations of PAI gene with eNOS and APOA5 were statistically very significant; however, the P values of the associated genotypic-combinations were identical or superior to those obtained by the simple analysis of each one of them, indicating that their actions on MI risk are likely to be independent. Conclusion MI is a multifactorial disease involving complex interactions of genetic factors and environmental conditions. Characterizing gene-gene interactions may be difficult due to the large number of candidate genes and the complex interactions among them, but as our results suggest, it is probably a more powerful approach to study complex diseases such as MI.