Association of Endothelial Nitric Oxide Synthase Gene Polymor-phisms with Early-Onset Ischemic Stroke in South Indians

Abstract

Aim:The aim of this study was to investigate the association of T-786C, G894T and 4a/b polymorphisms in the endothelial nitric oxide synthase (eNOS) gene with early-onset ischemic stroke in South Indians. Methods: We enrolled 177 patients diagnosed with ischemic stroke aged between 15 to 45 years and 219 age-and gender-matched healthy controls. Genotypes of eNOS T-786C, G894T and 4a/b were identified by polymerase chain reaction and restriction fragment length polymorphism. Results: The allele and genotype frequencies of eNOS 4a/b, T-786C and G894T did not differ significantly in the patient group compared to controls. Logistic regression analysis indicated the 4a allele to be an independent predictor of ischemic stroke in females (dominant model: OR, 2.46; 95% CI, 1.11 to 5.43; p 0.026). Marked differences were found in the prevalence of the minor alleles of the three variants when comparing the South Indian population with the reported frequencies from Caucasians. There was also a contrast in the frequencies of 4ab and T-786C variants from other Asians. The genotypes of all three variants were found to be in Hardy-Weinberg equilibrium. There was a lack of significant linkage disequilibria among the variants, and none of the estimated haplotypes increased or decreased the risk of ischemic stroke. Conclusion

Variants of the Endothelial Nitric Oxide Gene and Cerebral Blood Flow after Severe Traumatic Brain Injury

“…Relatively small studies have shown variable associations between individual NOS3 variants and NOS3 haplotypes with the risk of stroke (Howard et al, 2005;Majumdar et al, 2010;Saidi et al, 2010;Song et al, 2010;Yemisci et al, 2009). A meta-analysis of casecontrolled studies through 2008 examining the 894G > T and 27-bp VNTR variants of NOS3 in stroke suggested that the 4a allele was not associated with an increased risk, but that the 894T allele may have a marginally increased risk of stroke (odds ratio 1.14; 95% CI 0.99,1.31; Tao and Chen, 2009).…”

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

“…Only two studies, to the best of our knowledge, [11,16] performed in Caucasians have reported the role of NOS3 gene variations in determining the NO levels and their association with stroke. Two studies from South Asian-Indian population have also reported the association of some NOS3 gene SNPs with ischemic stroke but the studies were not elaborate and did not involve the evaluation of NO levels [18,19]. Our present study involved a comparative assessment of NO levels and NOS3 gene SNPs detected by SSCP, in young Asian Indian stroke patients and Table 3 Allelic and genotypic associations.…”

“…These metabolite levels have been previously shown to be associated with NOS3 SNPs [11]. However, only a limited number of studies have extensively looked at the possibility of NOS3 SNPs being a risk factor for ischemic stroke in young Asian Indian population [18,19]. The present study aimed at determining the role of NO levels and genetic variations in the NOS3 promoter/exonic regions towards the development of IS in young Asian Indians.…”

Detailed Analysis of Gene Polymorphisms Associated with Ischemic Stroke in South Asians

“…Relevant studies identified were; five for MTHFR C677T [22]–[26], three for PDE4D SNP 83 [27]–[29] and 2 studies each for eNOS 4a/4b [30], [31], ACE [32], [33], ApoE E4/E4 [34], [35], FVL G1691A [36], [37], PDE4D SNP 87 and 32 [38], [39] and IL10 [40], [41] genes. Two studies each reporting different stroke sub types (Cerebral Venous Thrombosis (CVT) and arterial paediatric ischemic stroke) were found for genes MTRR G66A [42], [43], MTR A2756G [42], [43], MTHFR A1298C [42], [43] and FVL A4070G [36], [42], [43], and therefore ORs for risk were not estimable.…”