Background. Progression of atherosclerosis, the main reason of cardiovascular diseases, depends on multiple genetic and environmental factors. Genetic susceptibility to CAD may be determined by specific polymorphic variants of genes encoding isoforms involved in processes important in the pathogenesis of atherosclerosis. Participation of single polymorphic variants is relatively small, however its significance may increase in the presence of specific genetic or environmental background. Peroxisome proliferator-activated receptor alpha (PPARα) is a ligand-activated transcription factor which regulates the expression of genes involved in lipid metabolism, monocyte recruitment and adhesion, foam cell formation. It has also anti-inflammatory and antioxidant properties. Therefore it is thought to regulate proatherosclerotic processes in the vessel wall. Methylenetetrahydrofolate reductase (MTHFR) is an enzyme which plays an important role in homocysteine (Hcy) metabolism. The 677C>T polymorphism of MTHFR gene results in a decrease of the enzyme activity that leads to mild hyperhomocysteinemia. Elevated plasma level of homocysteine has been recognized as an independent risk factor of cardiovascular disease.

Aim. The aim of the study was an evaluation a possible association between G>C intron 7 polymorphism of PPARA gene or 677C>T polymorphism of MTHFR gene and CAD, as well as analysis of interactions between polymorphic variants and conventional risk factors of CAD in determining the risk of the disease.

Methods. We studied 339 white Caucasians, including:177 patients with angiographically confirmed CAD and 162 blood donors without history of CAD. Polymorphisms were genotyped using RFLP-PCR (Restriction Fragments Lenght Polymorphism – Polymerase Chain Reaction) method. Data were analyzed using STATISTICA 6.0 and EpiInfo-6 (WHO) software.

Results. We did not observed the differences in the distribution of genotypes and alleles of MTHFR and PPARA genes. There were only tendency to higher prevalence of T and C alleles, respectively in CAD group. However we noticed significantly higher frequency of carriers of both “proatherosclerotic” variants in CAD group (19.2%) than in controls (8%) (p=0.004, OR=2.73). The PPARA gene polymorphism shows also cumulative and synergic effect on CAD with elevated level of triacylglycerols ( p=0.0004, OR=4.23, SIM=1.57) and overweight or obesity (p=0.0001, OR=3.62, SIM=2.8). The strongest influence on CAD was observed for carrier-state of PPARA C allele with carrier-state of MTHFR T allele and overweight or obesity (p=0.0002, OR=7.49, SIM=2.78).

Conclusions. The PPARA gene G>C polymorphism in intron 7 together with MTHFR gene 677C>T polymorphism may be regarded as a risk factor of premature CAD, especially in the presence of specific conventional risk factors.

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