Association of endothelial nitric oxide synthase polymorphisms with coronary artery disease in Korean individuals with or without diabetes mellitus

Abstract

Polymorphisms of the endothelial nitric oxide synthase (eNOS) gene have been implicated in various diseases, but their roles as risk factors in type 2 diabetes mellitus (T2DM) with regard to coronary artery disease (CAD) are largely unknown. Therefore, we investigated the association of the genotypes and haplotypes of eNOS polymorphisms in CAD with T2DM. A case-control study was performed to evaluate the genotypes and haplotypes of the eNOS polymorphisms (-786T>C, 4a4b and 894G>T) in 192 CAD patients and 196 controls. The same population was also re-organized upon the status of T2DM. The genotypes of eNOS -786T>C, 4a4b and 894G>T polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism. We found that eNOS -786TC+CC and 4a4b+4a4a genotypes were significantly prevalent in the diabetic controls and the diabetic CAD patients compared to the non-diabetic controls or non-diabetic CAD patients, respectively. The frequency of the -786C-4a-894G haplotype was significantly greater in the diabetic CAD patients (p=0.001) and diabetic controls (p=0.023) compared to the non-diabetic controls, whereas the haplotype of -786T-4b-894G was less prevalent in the diabetic CAD patients compared to the non-diabetic controls (p=0.018). Significant associations of the genotypes and the haplotypes were consistently observed in the T2DM group compared to non-DM group, regardless of CAD status. Our finding suggests that the eNOS -786T>C and 4a4b polymorphisms and the -786C-4a-894G haplotype are risk factors for T2DM, whereas the haplotype of -786T-4b-894G has a protective effect against the development of T2DM.