Interaction between COX-2 G-765C and smoking in relation to coronary artery disease in a Chinese Uighur population

Coronary artery disease (CAD) is a complex multifactorial and polygenic disorder where multiple environmental and genetic factors are involved simultaneously. The purpose of this study was to explore the relationship between the interaction of cyclooxygenase-2 (COX-2) gene polymorphism and smoking and CAD in a Uighur population.

Using a case-control study of Chinese Uighur CAD patients (n=430) and healthy controls (n=470), we investigated the roles of G-765C polymorphism in the COX-2 gene (PTGS2) by the use of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis.

The PTGS2 GG genotype was significantly more prevalent in CAD patients (84.6% vs. 78.3%; p=0.014). Multiple logistic regression analysis showed two independent risk factors: smoking (OR 1.89, 95% CI 1.01-5.24; p=0.008) and hypertension (OR 2.73, 95% CI 1.59-7.21; p=0.001). Moreover, there was a synergistic effect between smoking and the PTGS2 polymorphism and the occurrence of CAD (interaction p=0.009). The odds ratio (OR) estimated by the combined analysis of the PTGS2 GG genotype and smoking history (OR 4.09, 95% CI 2.7-9.3) was markedly higher than that estimated separately from the PTGS2 GG genotype (OR 1.28, 95% CI 0.8-1.9) or smoking (OR 2.51, 95% CI 1.5-5.7) alone. Plasma 6-keto-PGF1α, a stable metabolite of PGI(2), was lower in individuals with the PTGS2 GG genotype (p<0.05). Smoking could further lower plasma 6-keto-PGF1α concentrations in GG genotype carriers than non-smokers, especially in patients with CAD.

The PTGS2 polymorphism and smoking were synergistically and significantly associated in Chinese Uighur patients with CAD.