Genetic polymorphisms of eNOS (-786T/C, Intron 4b/4a & 894G/T) and its association with asymptomatic first degree relatives of coronary heart disease patients.

BACKGROUND: The eNOS gene has been extensively screened for important variations in the promoter (-786T/C), Intron 4 (4b/4a) and exon 7 (894G/T) regions in multiple diseases. Prevalence of Coronary Heart Disease (CHD) is much higher in young Indians when compared to other ethnic groups and first-degree relatives (FDRS) of CHD patients are at risk correlating with earlier age-of-onset and poor prognosis.

OBJECTIVE: The objective of this study is to understand the genetic mechanism of eNOS -786T/C, Intron 4b/4a and 894G/T polymorphisms/haplotypes in the development of CHD and to identify individuals having coronary risk factors among the FDRS of CHD patients by comparing them with the general population.

MATERIALS & METHODS: The study population consisted of 300 CHD patients with angiographically documented, 100 FDRS and 300 age and sex matched healthy controls. Genotyping of eNOS -786T/C, Intron 4b/4a was carried out by Allele specific-Polymerase Chain Reaction (As-PCR) and 894G/T by PCR-restriction fragment length polymorphism (PCR-RFLP) assays.

RESULTS: The frequency of risk factors for CHD includes age, blood pressure, obesity, diabetes mellitus, smoking, non-vegetarian diet, family history are higher in CHD patients and FDRS compared to controls (p < 0.01). The genotype distribution, allele frequencies and haplotypes of the eNOS -786T/C, 4b/4a and 894G/T were significantly different between CHD patients, FDRS and controls. eNOS gene haplotypes GCB, TCB (G-allele of 894G/T, C-allele -786T/C, B-allele of Intron 4b/4a respectively) were associated with high nitrite/nitrate levels compared to GTB in both FDRS and CHD patients (p < 0.01).

CONCLUSION: The study shows the importance of eNOS polymorphism in the pathogenesis of CHD and predicting the risk of future coronary events in asymptomatic healthy FDRS and suggests the use of new therapeutics and initiating the measures for prevention or delaying the progression of the disease by life style modification or treatment modalities in high-risk individuals.