Abstract

Myocardial infarction (MI), one of the most common manifestations of cardiovascular system aging, is often fatal. The vast majority of studies on genetic susceptibility to age-dependent diseases are carried out using the case–control study design. However, its use involves a number of difficulties, most of which arise when establishing the control group of relatively healthy individuals. In this work, survival functions were analyzed for carriers of alternative polymorphic variants of 18 genes that had been tested for association with MI using the case–control approach in our previous study, and the magnitude of the shift in the age of the disease onset depending on individual variations of the genome was estimated. The following risk variants were associated with the age of MI: rs2430561*A of IFNG (HR = 1.3, P = 0.043), rs1799889*5 of PAI-1 (HR = 1.3, P = 0.039), rs1800896*GG of IL10 (HR = 1.5, P = 0.0048), rs1800471*C of TGFB1 (HR = 1.5, P = 0.043), and rs11614913*TT of MIR196A2 (HR = 1.5, P = 0.035). In carriers of these variants, the disease developed 3‒6 years earlier than in carriers of alternative variants. The results of this study were compared with data on the associations with MI previously obtained on the same sample using the case–control approach. It turned out that the estimates based on the two methods mostly disagreed. However, the age-dependent approach relies on fewer assumptions that can be additionally verified. In our opinion, it makes this approach more promising than the case–control design.

中文翻译：

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年龄依赖性方法来寻找与心肌梗死相关的遗传变异

摘要

心肌梗塞（MI）是心血管系统衰老的最常见表现之一，通常是致命的。关于年龄依赖性疾病的遗传易感性的绝大多数研究是使用病例对照研究设计进行的。然而，其使用涉及许多困难，其中大多数是在建立相对健康个体的对照组时出现的。在这项工作中，分析了18种基因的多态变体的携带者的生存功能，这些变体已在我们先前的研究中使用病例对照方法进行了与MI的相关性测试，并且疾病发作年龄的变化幅度取决于估计基因组的个体变异。以下风险变量与MI的年龄有关：rs2430561 * A IFNG（HR = 1.3，P = 0.043），PAI-1的rs1799889 * 5 （HR  = 1.3，P = 0.039），IL10的rs1800896 * GG （HR = 1.5，P = 0.0048），TGFB1的rs1800471 * C （HR = 1.5 ，P  = 0.043）和MIR196A2的rs11614913 * TT （HR = 1.5，P= 0.035）。在这些变体的携带者中，该疾病比其他变体的携带者提前3-6年发展。这项研究的结果与以前使用病例对照方法从同一样本中获得的心梗相关性的数据进行了比较。事实证明，基于这两种方法的估计大部分不同。但是，基于年龄的方法依赖较少的假设，这些假设可以进一步验证。我们认为，这种方法比案例控制设计更有希望。