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Genetic polymorphism of CYP1A2 increases the risk of myocardial infarction.

机译:CYP1A2的遗传多态性增加了心肌梗死的风险。

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BACKGROUND: There is growing evidence that DNA damage caused by mutagens found in tobacco smoke may contribute to the development of coronary heart disease (CHD). In order to bind to DNA many mutagens require metabolic activation by cytochrome P450 (CYP) 1A1 or CYP1A2. The objective of this study was to determine the effects of CYP1A1 and CYP1A2 genotypes on risk of myocardial infarction (MI) and whether smoking interacts with genotype to modify risk. METHODS: Subjects (n = 873) with a first acute non-fatal MI and population based controls (n = 932) living in Costa Rica, matched for age, sex, and area of residence, were genotyped for CYP1A1*2A and CYP1A2*1F by restriction-fragment length polymorphism (RFLP)-PCR, and smoking status was determined by questionnaire. RESULTS: After adjusting for matching variables and potential confounders, no association was observed between CYP1A1 genotype and risk of MI. Compared to individuals with the high inducibility CYP1A2*1A/*1A genotype, the adjusted odds ratio and 95% confidence intervals for risk of MI were 1.19 (0.97 to 1.47) for the *1A/*1F genotype and 1.55 (1.10 to 2.18) for the *1F/*1F genotype. No significant interactions were observed between smoking and either CYP1A1 or CYP1A2 genotype. CONCLUSIONS: The low inducibility genotype for CYP1A2 was associated with an increased risk of MI. This effect was independent of smoking status and suggests that a substrate of CYP1A2 that is detoxified rather than activated may play a role in CHD.
机译:背景:越来越多的证据表明烟草烟雾中发现的诱变剂造成的DNA损伤可能有助于冠心病(CHD)的发育。为了与DNA结合许多诱变,需要通过细胞色素P450(CYP)1A1或CYP1A2来代谢激活。本研究的目的是确定CYP1A1和CYP1A2基因型对心肌梗死(MI)风险的影响,以及吸烟是否与基因型相互作用以改变风险。方法:受到居住在哥斯达黎加的第一急性非致命MI和基于群体的基于急性非致命MI和群体的对照(n = 932),符合年龄,性别和住宅面积,对CYP1A1 * 2A和CYP1A2 *进行基因分型。 1F通过限制性片段长度多态性(RFLP)-PCR,并通过问卷确定吸烟状态。结果:调整匹配变量和潜在混凝剂后,CYP1A1基因型与MI风险之间没有观察到任何关联。与具有高诱导性CYP1A2 * 1A / * 1A基因型的个体相比,用于* 1A / * 1F基因型和1.55(1.10至2.18)的调整后的差距和95%的置信度为1.19(0.97至1.47)(1.10至2.18)对于* 1F / * 1F基因型。吸烟与CYP1A1或CYP1A2基因型之间没有观察到显着的相互作用。结论:CYP1A2的低诱导性基因型与MI的风险增加有关。这种效果与吸烟状况无关,并表明解毒而不是激活的CYP1A2的基材可能在CHD中发挥作用。

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