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Genetic variance in CYP2C8 and increased risk of myocardial infarction.

机译:CYP2C8的遗传变异和心肌梗塞的风险增加。

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BACKGROUND: Epoxyeicosatrienoic acids (EETs) are important mediators in vasodilatation, acting as endothelium-derived hyperpolarizing factors. CYP2C enzymes catalyze the metabolism of arachidonic acid to EETs. Genetic variation within the genes encoding for these enzymes may result in differences in vascular response, among others in myocardial tissue, and may therefore increase the risk of myocardial infarction (MI). CYP2C8 and CYP2C9 are encoded by the genes of the same name. CYP2C9 polymorphisms have been associated with an increased risk of MI. As CYP2C8 is genetically linked to CYP2C9 and on account of its role in EET production, we hypothesized that CYP2C8 polymorphisms are associated with the risk of MI. METHODS: This study was embedded within the Rotterdam study, a prospective population-based cohort study. The study population included all participants with successful genotyping and without prevalent MI (n=5199). Twenty-five tagging single nucleotide polymorphisms within and around the gene-coding areas of CYP2C8 and CYP2C9 were tested for an association with incident MI using survival analysis techniques with multivariable adjustment for potential confounders. RESULTS: During follow-up, 290 persons developed an incident MI. One tag-SNP in the CYP2C8 gene was associated with incident MI after Bonferroni correction, rs1058932C>T (variant genotype hazard ratio 1.54; 95% CI: 1.22-1.95). There was a significant gene-sex interaction with a relative excess risk of 1.40 (95% CI: 0.33-2.47) for men. CONCLUSION: SNP rs1058932C>T within the CYP2C8 gene is associated with an increased risk of MI, which is, possibly because of a vascular effect of sex steroids, highest in males.
机译:背景:环氧二十碳三烯酸(EETs)是血管舒张中的重要介体,是内皮衍生的超极化因子。 CYP2C酶催化花生四烯酸代谢为EET。编码这些酶的基因内的遗传变异可能导致血管反应的差异,尤其是在心肌组织中,因此可能增加心肌梗塞(MI)的风险。 CYP2C8和CYP2C9由同名基因编码。 CYP2C9多态性与MI风险增加有关。由于CYP2C8与CYP2C9遗传相关,并且由于其在EET产生中的作用,我们假设CYP2C8多态性与MI的风险有关。方法:该研究嵌入在鹿特丹研究中,这是一项基于人群的前瞻性队列研究。研究人群包括所有成功进行基因分型且无普遍性心梗的参与者(n = 5199)。使用生存分析技术对潜在混杂因素进行多变量调整,对CYP2C8和CYP2C9基因编码区内和周围的二十五个标签单核苷酸多态性与事件MI的关系进行了测试。结果:在随访期间,有290人发生了MI事件。 CYP2C8基因中的一个标签SNP与Bonferroni校正后的事件MI相关联,即rs1058932C> T(变异基因型危险比1.54; 95%CI:1.22-1.95)。男性之间存在显着的基因-性别相互作用,相对过量风险为1.40(95%CI:0.33-2.47)。结论:CYP2C8基因内的SNP rs1058932C> T与MI风险增加有关,这可能是由于性类固醇的血管作用引起的,在男性中最高。

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