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

Abstract

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.