Lack of Association between Endothelial Nitric Oxide Synthase Gene Polymorphisms and Coronary Artery Disease among Egyptian Population

Abstract

Controversial results regarding the association of e NOS gene polymorphisms with Coronary Artery Disease (CAD) have been reported up to now, there has been conflicting data regarding the association between two clinically relevant polymorphisms (T-786C) in the promoter region and intron 4 variable number of 27-bp tandem repeats (VNTR) of the eNOS gene and  coronary artery disease (CAD). The present study was undertaken to investigate association of these two eNOS gene polymorphisms with susceptibility to CAD in Egyptian population. A total of 80 patients with CAD and 40 healthy controls were included in this study. CAD patients were divided according to their body mass index (BMI) limits into 2 main groups: normal weigh group (BMI: 18.5–24.9, n=40) and abnormal weight group (BMI≥25, n= 40), the last group was further sub-divided into overweight group (BMI: 25.0–29.9, n= 20) and obese group (BMI≥ 30, n= 20). The T-786C and intron 4 VNTR polymorphisms were analyzed by polymerase chain reaction (PCR) using specific primers. The T-786C polymorphism frequencies for T/T, T/C and C/C genotypes were 27.5%, 28.75%, 43.75% respectively in the CAD patients, and 35%, 37.5%, 27.5% in  the control subjects, while allele frequencies for C, T were  58.12%, 41.87% in the CAD patients and 46.25%, 53.75%, in the control group. No significant differences were observed in genotype frequencies between CAD patient group when compared to control group, or between them according to allele frequency. Also, there was no significant differences in the genotype distribution and allele frequencies of T786-C polymorphism among the overweight and obese cases compared to normal weight subjects. The genotype frequencies for eNOS b/b, a/b, a/a were 45%, 50% and 5% in the CAD patients, and 35%, 65% and 0% in the control subjects, with no significant difference between the two groups. Also, there were no significant difference in the allele frequencies between the CAD patients (a: b = 30%:70%), and controls (a: b = 32.5%:67.5%) as well as in the distribution of genotype and alleles frequencies of intron 4 VNTR of eNOS gene when overweight and obese patient groups were compared with the normal weight patient group. Thus the present study suggested that the two eNOS gene polymorphisms (the eNOS T-786C and intron 4 VNTR polymorphisms) were unlikely to be major genetic susceptibility factors for CAD in the Egyptian population even after classification of the CAD patients according to their BMI. Further studies with larger sample size are required to be done to confirm these findings.