Role of Endothelial Nitric Oxide Synthase Gene Polymorphisms in Predicting Aneurysmal Subarachnoid Hemorrhage in South Indian Patients

Abstract

Endothelial nitric oxide synthase (eNOS) gene polymorphisms have been implicated as predisposing genetic factors that can predict aneurysmal subarachnoid hemorrhage (aSAH), but with controversial results from different populations. Using a case-control study design, we tested the hypothesis whether variants in eNOS gene can increase risk of aSAH among South Indian patients, either independently, or by interacting with other risk factors of the disease. We enrolled 122 patients, along with 224 ethnically matched controls. We screened the intron-4 27-bp VNTR, the promoter T-786C and the exon-7 G894T SNPs in the eNOS gene. We found marked interethnic differences in the genotype distribution of eNOS variants when comparing the South Indian population with the reported frequencies from Caucasian and Japanese populations. Genotype distributions in control and patient populations were found to be in Hardy-Weinberg equilibrium. In patients, the allele, genotype and estimated haplotype frequencies did not differ significantly from the controls. Multiple logistic regression indicated hypertension and smoking as risk factors for the disease, however the risk alleles did not have any interaction with these risk factors. Although the eNOS polymorphisms were not found to be a likely risk factor for aSAH, the role of factors such as ethnicity, gender, smoking and hypertension should be evaluated cautiously to understand the genotype to phenotype conversion.

Association of eNOS and ACE gene polymorphisms and plasma nitric oxide with risk of non‐small cell lung cancer in South India

“…The impact of smoking and eNOS gene polymorphism on the risk of developing pulmonary diseases, such as coronary artery disease, ischemic stroke, hypertension, and myocardial infraction, was reported . In the Indian context too, only the effect of eNOS gene polymorphism on ischemic stroke and aneurysmal subarachnoid hemorrhage was reported.…”

Risk Factors for Aneurysmal Subarachnoid Hemorrhage in an Indian Population

“…Nonreplication of genetics association studies could be attributed to these environmental variables, in addition to ethnicity [21]. The biological impact of hypertension has been proposed to be involved in the formation and progression of IA resulting in aSAH.…”

Association Between Three eNOS Polymorphisms and Intracranial Aneurysms Risk

“… 18 Khurana et al 24 first investigated the relationship between the T786C polymorphism and IA susceptibility and no significant association was found. After that, 9 studies from 8 articles had been done, 26 – 30 , 32 – 34 and the result of 5 studies was negative. 27 , 30 , 32 – 34 The other 4 Asian studies have analyzed genotype of cases and controls but did not conclude the association.…”