Endothelial nitric oxide synthase Glu298Asp, 4b/a,and −786T>C gene polymorphisms and the risk of ischemic stroke

Saidi S, Mallat SG, Almawi WY, Mahjoub T. Endothelial nitric oxide synthase Glu298Asp, 4b/a, and ?786T>C gene polymorphisms and the risk of ischemic stroke
Acta Neurol Scand: 2010: 121: 114–119.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Background and purpose – Endothelial nitric oxide synthase (eNOS) gene polymorphisms were associated with reduced NO production, and were evaluated as risk factors for ischemic stroke (IS). We investigated the association between eNOS gene ?786T>C (promoter), 27‐bp repeat 4b/4a (intron 4), and Glu298Asp (exon 7) polymorphisms with IS in 329 IS patients and 444 controls. Materials and methods – Glu298Asp and ?786T>C genotyping was done by PCR‐RFLP, 4b/4a was assessed by PCR–ASA. The contribution of eNOS polymorphisms to IS was analyzed by haplotype and multivariate regression analysis. Results – Higher frequency of 298Asp allele was seen in IS patients (P = 1.2 × 10^?10), which remained independently associated with IS on multivariate analysis after controlling for traditional cerebrovascular risk factors. Allele and genotype distribution of 4b/4a and ?786T>C polymorphisms were comparable between patient and controls. Significantly higher prevalence of 298Asp/4b/?786T and 298Asp/4b/?786C haplotypes were seen in IS cases, thus conferring a disease susceptibility nature to these haplotypes. Multivariate regression analysis confirmed the association of 298Asp/4b/?786T and 298Asp/4b/?786C haplotypes, and in addition identified 298Asp/4a/?786T haplotype to be independently associated with IS, after controlling for traditional cerebrovascular risk factors. Conclusions – Genetic variation at the eNOS locus represent genetic risk factor for increased susceptibility to IS.