Titov Boris V, Osmak German J, Matveeva Natalia A, Kukava Nino G, Shakhnovich Roman M, Favorov Alexander V, Ruda Mikhail Ya, Favorova Olga O
Institute of Experimental Cardiology, Russian Cardiology Scientific and Production Center, Moscow, Russia.
Department of Molecular Biology and Medical Biotechnology, Pirogov Russian National Research Medical University, Moscow, Russia.
Mol Biol Rep. 2017 Aug;44(4):315-321. doi: 10.1007/s11033-017-4112-5. Epub 2017 Jul 6.
Epidemiological genetics established that heritability in determining the risk of myocardial infarction (MI) is substantially greater when MI occurs early in life. However, the genetic architecture of early-onset and late-onset MI was not compared. We analyzed genotype frequencies of SNPs in/near 20 genes whose protein products are involved in the pathogenesis of atherosclerosis in two groups of Russian patients with MI: the first group included patients with age of first MI onset <60 years (N = 230) and the second group with onset ≥60 years (N = 174). The control group of corresponding ethnicity consisted of 193 unrelated volunteers without cardiovascular diseases (93 individuals were over 60 years). We found that in the group of patients with age of onset <60 years, SNPs FGB rs1800788T, TGFB1 rs1982073T/T, ENOS rs2070744C and CRP rs1130864T/T were associated with risk of MI, whereas in patients with age of onset ≥60 years, only TGFB1 rs1982073T/T was associated with risk of MI. Using APSampler software, we found composite markers associated with MI only in patients with early onset: FGB rs1800788T + TGFB1 rs1982073T; FGB rs1800788T + LPL rs328C + IL4 rs2243250C; FGB rs1800788T + ENOS rs2070744C (Fisher p values of 1.4 × 10 to 2.2 × 10; the permutation p values of 1.1 × 10 to 3.0 × 10; ORs = 2.67-2.54). Alleles included in the combinations were associated with MI less significantly and with lower ORs than the combinations themselves. The result showed a substantially greater contribution of the genetic component in the development of MI if it occurs early in life, and demonstrated the usefulness of genetic testing for young people.
流行病学遗传学研究表明，在心肌梗死（MI）发病风险的决定因素中，遗传度在年轻时发生MI的情况下显著更高。然而，早发型和晚发型MI的遗传结构并未进行比较。我们分析了两组俄罗斯MI患者中20个基因内部或附近单核苷酸多态性（SNP）的基因型频率，这些基因的蛋白质产物参与动脉粥样硬化的发病机制：第一组包括首次MI发病年龄小于60岁的患者（N = 230），第二组发病年龄≥60岁（N = 174）。相应种族的对照组由193名无心血管疾病的无关志愿者组成（93人年龄超过60岁）。我们发现，在发病年龄小于60岁的患者组中，SNP FGB rs1800788T、TGFB1 rs1982073T/T、ENOS rs2070744C和CRP rs1130864T/T与MI风险相关，而在发病年龄≥60岁的患者中，只有TGFB1 rs1982073T/T与MI风险相关。使用APSampler软件，我们发现仅在早发型患者中存在与MI相关的复合标记：FGB rs1800788T + TGFB1 rs1982073T；FGB rs1800788T + LPL rs328C + IL4 rs2243250C；FGB rs1800788T + ENOS rs2070744C（Fisher p值为1.4×10至2.2× 10；置换p值为1.1×10至3.0×10；比值比=2.67 - 2.54）。组合中包含的等位基因与MI的关联程度低于组合本身，且比值比更低。结果表明，如果MI在年轻时发生，遗传成分在其发病过程中的作用显著更大，并且证明了对年轻人进行基因检测的有用性。
