Endothelial nitric oxide synthase Glu298Asp, 4b/a, and −786T>C gene polymorphisms and the risk of ischemic stroke
October 6th, 2009 Posted by: admin
Saidi S, Mallat SG, Almawi WY, Mahjoub T. Endothelial nitric oxide synthase Glu298Asp, 4b/a, and [minus]786T>C gene polymorphisms and the risk of ischemic strokeActa Neurol Scand: DOI: 10.1111/j.1600-0404.2009.01192.x.© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard.Background and purpose [ndash] 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 [minus]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 [ndash] Glu298Asp and [minus]786T>C genotyping was done by PCR-RFLP, 4b/4a was assessed by PCR[ndash]ASA. The contribution of eNOS polymorphisms to IS was analyzed by haplotype and multivariate regression analysis.Results [ndash] Higher frequency of 298Asp allele was seen in IS patients (P = 1.2 × 10[minus]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 [minus]786T>C polymorphisms were comparable between patient and controls. Significantly higher prevalence of 298Asp/4b/[minus]786T and 298Asp/4b/[minus]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/[minus]786T and 298Asp/4b/[minus]786C haplotypes, and in addition identified 298Asp/4a/[minus]786T haplotype to be independently associated with IS, after controlling for traditional cerebrovascular risk factors.Conclusions [ndash] Genetic variation at the eNOS locus represent genetic risk factor for increased susceptibility to IS.
