Ischemic stroke is a leading cause of death throughout the world. An increasing number of studies have suggested that genetic factors are important in the stroke risk. The aim of our study was to investigate whether the Variable Number of Tandem Repeats (VNTR) polymorphism in intron 4 of the endothelial nitric oxide synthase (eNOS) gene is associated with ischemic stroke in a South Indian population. 357 patients and 283 controls were enrolled in this case-control study. The ischemic stroke patients were classified according to TOAST classification. The eNOS gene polymorphism was determined by polymerase chain reaction-polyacrylamide gel electrophoresis. The genotypes were confirmed by sequencing the PCR products. There were significant differences in the genotype and allele frequencies of eNOS polymorphism between the patients with ischemic stroke and healthy controls (p=0.000). Multiple logistic regression analysis with forward stepwise selection using the potential confounders (sex, age, diabetes, hypertension, smoking and alcoholism) and eNOS gene variant revealed that the VNTR polymorphism in intron 4 of the eNOS gene is significantly [adjusted odds ratio=6.23, 95%CI (4.30-9.29), p=0.000] associated with ischemic stroke in the South Indian population from Andhra Pradesh. We did not find significant association of this polymorphism with any specific stroke subtype. Further hypertensives bearing 4a allele in high frequency are more predisposed to stroke.
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