Background. Progression of atherosclerosis is the main cause of coronary artery disease (CAD). It results from the interaction between multiple genetic and non-genetic factors combinations. Genetic predisposition to the disease may be co-created by functional polymorphic genes, encoding variants of proteins with altered biological activity that are involved in the processes important for the pathogenesis of atherosclerosis. Polymorphic variants of genes encoding markers of proinflammatory state, such as interleukin-6 (IL-6) and prothrombotic state, such as plasminogen activator inhibitor-1 (PAI-1) may determine a susceptibility to the disease.

Aim. The aim of the study was to assess a relationships between single genetic polymorphisms of IL-6 and PAI-1 and effects between polymorphic variants of these genes and cigarette smoking and CAD.

Material and Methods. The study was performed on 394 white Caucasians, including: 191 patients with angiographically documented CAD (aged 43.8±6.1, 64 femals and 127 males) and 203 blood donors (aged 35.3±10.5, 49 femals and 154 males) with no signs of CAD in the interview. Genetic polymorphisms analysis was performed using PCR-RFLP method. Data were analyzed using STATISTICA 6.0 and EPI-INFO (WHO) software.

Results. The genotypes frequencies were in agreement with Hardy-Weinberg equilibrium. We observed higher frequency of 5G allele of –674_–675insG polymorphism of PAI-1 gene in CAD patients than in controls (47.6% vs 40.4%) (p=0.04, OR=1.34 95%CI 1.00-1.80). 5G allele carriers (4G5G+5G5G genotypes) were more frequent in CAD group (74.3%) compared to controls (66.0%) (p= 0.048, OR=1.77 95%CI 1.00-3.14). In CAD female subgroup carriers of 5G allele were significantly more frequent than in female blood donors (78.1% vs. 57.1%) (p=0.031, OR=5.51 95%CI 1.13-26.78). We did not observed correlation between IL-6 –174G>C polymorphism and CAD. The frequency of IL-6 C allele was significantly higher only in male CAD subgroup (51.2%) compared to male blood donors (42.2%) (p=0.035, OR=1.44 95%CI 1.01-2.05). Contemporaneous carrier-state of PAI-1 5G allele and IL-6 C allele did not differentiate analyzed groups. In spite of rather weak association between analyzed polymorphic variants and the disease we found cumulative effects between specific genotype patterns and smoking in determining CAD, especially for PAI-1(4G5G+5G5G), IL-6(CC) and smoking (p=0.0001, OR=11.02 95%CI 2.36-70.99). There was also observed quite strong synergistic effect between homozygous CC of IL-6 gene and carriers of 5G allele of PAI-1 gene and smoking (synergy index SIM=3.71). The SIM value indicates that effect of both genetic and non-genetic factors on CAD is almost four-fold stronger than the effects of these factors considering separately.

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