Research Unit of Hematological and Autoimmune Diseases, Faculty of Pharmacy, University of Monastir, Tunisia.
Acta Neurol Scand. 2010 Feb;121(2):114-9. doi: 10.1111/j.1600-0404.2009.01192.x. Epub 2009 Oct 5.
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.
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.
Higher frequency of 298Asp allele was seen in IS patients (P = 1.2 x 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.
Genetic variation at the eNOS locus represent genetic risk factor for increased susceptibility to IS.
内皮型一氧化氮合酶（eNOS）基因多态性与 NO 生成减少有关，并被评估为缺血性卒中（IS）的危险因素。我们研究了 eNOS 基因-786T>C（启动子）、27 碱基对重复 4b/4a（内含子 4）和 Glu298Asp（外显子 7）多态性与 329 例 IS 患者和 444 例对照者 IS 之间的关系。
通过 PCR-RFLP 检测 Glu298Asp 和-786T>C 基因型，通过 PCR-ASA 评估 4b/4a。通过单体型和多变量回归分析来分析 eNOS 多态性对 IS 的贡献。
IS 患者中 298Asp 等位基因的频率更高（P = 1.2 x 10(-10)），在控制传统脑血管危险因素后，多变量分析仍与 IS 独立相关。4b/4a 和-786T>C 多态性的等位基因和基因型分布在患者和对照组之间无差异。IS 病例中 298Asp/4b/-786T 和 298Asp/4b/-786C 单体型的患病率显著更高，因此这些单体型具有疾病易感性。多变量回归分析证实了 298Asp/4b/-786T 和 298Asp/4b/-786C 单体型的相关性，并且在控制传统脑血管危险因素后，还确定了 298Asp/4a/-786T 单体型与 IS 独立相关。
eNOS 基因座的遗传变异是增加 IS 易感性的遗传危险因素。
