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

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.