Université de Tunis El Manar, Hôpital la Rabta, Service de Biochimie, LR99ES11, 1007 Tunis, Tunisie.
Cytokine. 2013 Dec;64(3):646-51. doi: 10.1016/j.cyto.2013.09.005. Epub 2013 Oct 3.
Controversial results regarding the association of eNOS gene (NOS3) polymorphisms with myocardial infarction (MI) have been reported. This study investigated the relationship of the -786T>C (rs2070744), 894G>T (rs1799983) and 4a4b polymorphisms of the NOS3 gene with the presence of MI in the Tunisian population. In addition, we also examined the association of NOS3 gene haplotypes with MI in Tunisian subjects. A total of 303 patients with MI and 225 controls were included in the study. The 894G>T and -786T>C single nucleotide polymorphisms were analyzed by PCR-RFLP, and 4a4b polymorphism just for PCR. There was significant linkage disequilibrium between the three NOS3 polymorphisms (p<0.0001). The genotype distribution and allele frequency of NOS3 4a4b, but not -786T>C and 894G>T, polymorphism was significantly different between MI patients and controls. The univariate logistic regression analysis showed a significant association of the 4a4b polymorphism and MI according to co-dominant, dominant and recessive models (co-dominant model OR: 4.38, 95%CI: 1.24-15.41; p=0.021, dominant model OR: 1.66, 95%CI: 1.14-2.42); p=0.007, and recessive model OR: 3.85, 95%CI: 1.10-13.47; p=0.035). The multivariate analysis, adjusted for traditional cardiovascular risk factors, revealed that the NOS3 4a4a genotype was an independent predisposing factor to MI, according to the models considered. In addition, a haplotype 7 (C-T-4a), (OR=12.05, p=0.010) was a risk factor of MI after controlling for classical risk factors. These finding suggest that the 4a4b polymorphism of the NOS3 gene was associated with MI in Tunisian patients.
关于内皮型一氧化氮合酶(NOS3)基因多态性与心肌梗死(MI)之间的关联,已有争议结果报道。本研究调查了 NOS3 基因的-786T>C(rs2070744)、894G>T(rs1799983)和 4a4b 多态性与突尼斯人群 MI 存在之间的关系。此外,我们还研究了 NOS3 基因单体型与突尼斯患者 MI 之间的关联。共纳入 303 例 MI 患者和 225 例对照。通过 PCR-RFLP 分析 894G>T 和-786T>C 单核苷酸多态性,PCR 分析 4a4b 多态性。NOS3 三种多态性之间存在显著连锁不平衡(p<0.0001)。NOS3 4a4b 基因型分布和等位基因频率在 MI 患者和对照组之间存在显著差异,但-786T>C 和 894G>T 多态性无差异。单变量 logistic 回归分析显示,4a4b 多态性与 MI 存在显著关联,根据共显性、显性和隐性模型(共显性模型 OR:4.38,95%CI:1.24-15.41;p=0.021,显性模型 OR:1.66,95%CI:1.14-2.42;p=0.007,隐性模型 OR:3.85,95%CI:1.10-13.47;p=0.035)。调整传统心血管危险因素后,多变量分析显示,NOS3 4a4a 基因型是 MI 的独立危险因素,考虑到所考虑的模型。此外,在控制经典危险因素后,单体型 7(C-T-4a)(OR=12.05,p=0.010)是 MI 的危险因素。这些结果表明,NOS3 基因的 4a4b 多态性与突尼斯患者的 MI 相关。