Goncharova I A, Nazarenko M S, Babushkina N P, Markov A V, Pecherina T B, Kashtalap V V, Tarasenko N V, Ponasenko A V, Barbarash O L, Puzyrev V P
Research Institute for Medical Genetics, Tomsk, 634050 Russia.
Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo, 650002 Russia.
Mol Biol (Mosk). 2020 Mar-Apr;54(2):224-232. doi: 10.31857/S0026898420020044.
The aim of the study was to identify the features of the genetic structure of myocardial infarction (MI) susceptibility depending on age ("early MI" denoting individuals who had the first MI before the age of 60 years, and "late MI" the group of patients with the first "MI after 60 years"). A total of 355 patients were examined (n = 121 early MI and n = 234 late MI) and 285 residents of the Siberian region (as a control group). Genotyping of 58 single nucleotide variants (SNPs) was performed using mass spectrometry using the Agena (ex Sequenom) MassARRAY® System. Statistical analysis was performed using Statistica 8.0 ("StatSoft Inc.", USA), as well as the "stats" and "genetics" packages in the R environment. The regulatory potential of SNPs was evaluated using the rSNPBase online service (http://rsnp.psych.ac.cn/). eQTL loci were identified using data from the Genotype-Tissue Expression (GTEx) project (http://www.gtexportal.org/) and the Blood eQTL online service (https://genenetwork.nl/bloodeqtlbrowser/). The GG genotype of ITGA4 rs1143674, the CC genotype of CDKN2B-AS1 rs1333049, and the CC genotype of KIAA1462 rs3739998, are generally associated with MI. The AA genotype of ADAMDEC1 rs3765124 (OR = 2.03; 95% CI 1.23-3.33; p = 0.004) and the GG genotype of AQP2 rs2878771 (OR = 2.24; 95% CI 1.23-4.09; p = 0.006) are associated with the development of MI at an early age, and the TT genotype of TAS2R38 rs1726866 (OR = 1.82; 95% CI 1.11-2.89; p = 0.009) was the high-risk genotype for the late MI. Genetic variants associated with MI are regulatory SNP (rSNP) and affect the affinity of DNA binding to transcription factors, carry out post-transcriptional control of gene activity and change the level of gene expression in various tissues. Thus, early and late MI are based on both common genetic variants of ITGA4, CDKN2B-AS1, KIAA1462 genes and specific ones (ADAMDEC1 and AQP2 for early MI and TAS2R38 for late MI).
本研究的目的是确定根据年龄划分的心肌梗死（MI）易感性的遗传结构特征（“早发性MI”指首次发生MI在60岁之前的个体，“晚发性MI”指首次发生MI在60岁之后的患者组）。共检查了355例患者（n = 121例早发性MI和n = 234例晚发性MI）以及285名西伯利亚地区居民（作为对照组）。使用Agena（原Sequenom）MassARRAY®系统通过质谱法对58个单核苷酸变异（SNP）进行基因分型。使用Statistica 8.0（美国“StatSoft公司”）以及R环境中的“stats”和“genetics”软件包进行统计分析。使用rSNPBase在线服务（http://rsnp.psych.ac.cn/）评估SNP的调控潜力。使用来自基因型-组织表达（GTEx）项目（http://www.gtexportal.org/）和血液eQTL在线服务（https://genenetwork.nl/bloodeqtlbrowser/）的数据鉴定eQTL位点。ITGA4 rs1143674的GG基因型、CDKN2B-AS1 rs1333049的CC基因型和KIAA1462 rs3739998的CC基因型通常与MI相关。ADAMDEC1 rs3765124的AA基因型（OR = 2.03；95%CI 1.23 - 3.33；p = 0.004）和AQP2 rs2878771的GG基因型（OR = 2.24；95%CI 1.23 - 4.09；p = 0.006）与早发性MI的发生相关，而TAS2R38 rs1726866的TT基因型（OR = 1.82；95%CI 1.11 - 2.89；p = 0.009）是晚发性MI的高危基因型。与MI相关的遗传变异是调控性SNP（rSNP），影响DNA与转录因子结合的亲和力，对基因活性进行转录后控制并改变各种组织中的基因表达水平。因此，早发性和晚发性MI既基于ITGA4、CDKN2B-AS1、KIAA1462基因的常见遗传变异，也基于特定的遗传变异（早发性MI为ADAMDEC1和AQP2，晚发性MI为TAS2R38）。
