Screening of the NOS3 gene identifies the variants 894G/T, 1998C/G and 2479G/A to be associated with acute onset ischemic stroke in young Asian Indians

• It is an association study.
• Out of 8 SNPs 3 SNPs showed the strongest association with the disease phenotype.
• SNPs 894G/T and 2479G/A showed association with NOx levels as well.
• Above SNPs represent genetic risk factor for acute ischemic stroke in Young Asian Indians.
• Haplotypic analysis further confirmed the single marker as well as multimaker association.

IntroductionNitric oxide levels and NOS3 gene variants play a pivotal role in the development of vascular diseases/stroke. We attempted to determine the role of NOS3 gene variants and plasma NO levels towards the development of ischemic stroke in young Asian-Indians.MethodsOne hundred ischemic stroke patients and 200 age and sex matched control study subjects were screened for NOS3 gene variants using SSCP [single stranded confirmation polymorphism] and PCR based techniques. Plasma NO metabolites [NOx] were evaluated for the investigated population.ResultsSignificantly higher NOx levels were observed in controls [controls 56.63 ± 25.92 μmol/L, patients 34.73 ± 19.88 μmol/L, p < 0.001]. The SNPs [single nucleotide polymorphisms] 894G/T, 1998C/G and 2479G/A were found associated with the disease phenotype with the most significant finding observed for 894G/T [χ2 = 36.68, p < 0.001]. The SNPs 894G/T and 2479G/A were significantly associated with NOx levels [p = 0.001]. The haplotypes TCA and TGA were overrepresented in the patient population [p < 0.0001].ConclusionTwo NOS3 SNP [894G/T and 2479G/A] variants and NOx levels are associated with ischemic stroke in young Asian Indians. These NOS3 SNPs might represent genetic risk factors for ischemic stroke in young Asian Indians. However these observations need to be confirmed by larger replicate/cross-sectional studies.