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Endothelial nitric oxide synthase Glu298Asp, 4b/a, and −786T>C gene polymorphisms and the risk of ischemic stroke
Author(s) -
Saidi S.,
Mallat S. G.,
Almawi W. Y.,
Mahjoub T.
Publication year - 2010
Publication title -
acta neurologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.967
H-Index - 95
eISSN - 1600-0404
pISSN - 0001-6314
DOI - 10.1111/j.1600-0404.2009.01192.x
Subject(s) - haplotype , enos , genotype , medicine , genotyping , allele , biology , allele frequency , genetics , stroke (engine) , gastroenterology , endocrinology , nitric oxide synthase , gene , nitric oxide , mechanical engineering , engineering
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.