Synergistic effects of the polymorphisms in the PAI-1 and IL-6 genes with smoking in determining their associated risk with coronary artery disease.

Objectives: To assess the relationship between IL-6 and PAI-1 polymorphisms and coronary artery disease (CAD) and to observe the interactions between these polymorphic variants and smoking in the CAD risk.

Design And Method: The study population consisted of 178 patients with angiographically documented CAD and 202 blood donors. The analyses of genetic polymorphisms were performed using the PCR-RFLP method.

Results: The frequency of PAI-1 5G allele was higher in the entire CAD group than in control group (p=0.04, OR=1.35). Also the 5G allele carriers (4G5G+5G5G) were more frequent in patients than in controls (p=0.03, OR=1.93). The number of women carrying 5G allele was again significantly higher among patients (OR=10.95 p=0.0075). The IL-6 C allele frequency was higher only in the CAD male subgroup (p=0.035, OR=1.44). We found synergistic and cumulative effects between specific genotype patterns and smoking in determining the risk of CAD, especially between PAI-1(4G5G+5G5G)+IL-6(CC) and smoking (SIM=4.18 and p=0.0005, OR=9.20, respectively).

Conclusions: There are synergistic and cumulative effects of 5G allele of PAI-1 polymorphism and C allele of IL-6 polymorphism with smoking in determining their associated risk with CAD.