Goncharova I A, Pecherina T B, Markov A V, Kashtalap V V, Tarasenko N V, Puzyrev V P, Barbarash O L
Research Institute of Medical Genetics.
"Research Institute for Complex Issues of Cardiovascular Diseases", Federal Agency for Scientific Organizations.
Kardiologiia. 2018 Aug(8):33-44.
To study associations between genes of different functional classes, including fibrogenesis genes, with coronary atherosclerosis and specific features of its course.
We included in this study 404 patients with confirmed chronic ischemic heart disease (IHD) who had undergone coronary artery bypass grafting. Two groups of participants were distinguished - those with (n=188) and without (n=216) history of myocardial infarction (MI). Control group consisted of inhabitants of the Siberia region (n=285). Associations were analyzed using 48 single nucleotide polymorphisms (SNP) located in genes earlier determined as associated with diseases of the cardiovascular continuum (diabetes mellitus, MI, atherosclerosis). Multiplex genotyping was performed using mass spectrometry. For statistical analyses we used Statistica v8.0 and R-language with "stats" and "genetics" packages.
We identified several genetic markers contributing to susceptibility to development of atherosclerosis. Same markers were identified as determinants of the character of the course of atherosclerotic disease. Risk of development of atherosclerosis was higher in carriers of the following genotypes: TT of ITGB5 gene (rs1007856) - by 1.6 times (OR=1.59; р=0.0153); GG of ITGA4 gene - by 1.85 times (OR=1.85; р=0.0016); GG of IGFBP7 gene (rs11133482) - by 2.4 times (OR=2.36; р=0.0031). The following genotypes were identified as protective against MI and determining stable course of the disease: AA of TLR4 gene (rs4986790) (OR=0.47; р=0.0104).; CC of LDLR gene (rs2738446) (OR=0,53; р=0.0041); GG of OAS1 gene (rs1131454) (OR=0.50; р=0.0274).
Susceptibility to coronary atherosclerosis and prognosis of disease progression were found to be associated with polymorphism of certain genes, involved in metabolism of the extracellular matrix and processes of fibrogenesis (ADAMDEC1, ITGA4, ITGB5, CDKN2B-AS1, IGFBP7), lipid metabolism (LDLR), immune system functioning (TLR4, OAS1) and DNA repair (LIG1).
研究不同功能类别的基因（包括纤维生成基因）与冠状动脉粥样硬化及其病程的特定特征之间的关联。
本研究纳入了404例确诊为慢性缺血性心脏病（IHD）且接受过冠状动脉搭桥术的患者。将参与者分为两组——有心肌梗死（MI）病史的（n = 188）和无心肌梗死病史的（n = 216）。对照组由西伯利亚地区的居民组成（n = 285）。使用位于先前确定与心血管连续疾病（糖尿病、MI、动脉粥样硬化）相关的基因中的48个单核苷酸多态性（SNP）分析关联。采用质谱法进行多重基因分型。我们使用Statistica v8.0和带有“stats”及“genetics”软件包的R语言进行统计分析。
我们鉴定出了几个促成动脉粥样硬化易感性的遗传标记。相同的标记被确定为动脉粥样硬化疾病病程特征的决定因素。以下基因型的携带者发生动脉粥样硬化的风险更高：整合素β5（ITGB5）基因（rs1007856）的TT基因型——高1.6倍（OR = 1.59；p = 0.0153）；整合素α4（ITGA4）基因的GG基因型——高1.85倍（OR = 1.85；p = 0.0016）；胰岛素样生长因子结合蛋白7（IGFBP7）基因（rs11133482）的GG基因型——高2.4倍（OR = 2.36；p = 0.0031）。以下基因型被确定为对MI有保护作用并决定疾病的稳定病程：Toll样受体4（TLR4）基因（rs4986790）的AA基因型（OR = 0.47；p = 0.0104）；低密度脂蛋白受体（LDLR）基因（rs2738446）的CC基因型（OR = 0.53；p = 0.0041）；2'-5'-寡腺苷酸合成酶1（OAS1）基因（rs113,1454）的GG基因型（OR = 0.50；p = 0.0274）。
发现冠状动脉粥样硬化的易感性和疾病进展的预后与某些参与细胞外基质代谢和纤维生成过程（解整合素和金属蛋白酶结构域含蛋白10（ADAMDEC1）、整合素α4（ITGA4）、整合素β5（ITGB5）、细胞周期蛋白依赖性激酶抑制剂2β反义RNA1（CDKN2B-AS1）、胰岛素样生长因子结合蛋白7（IGFBP7））、脂质代谢（低密度脂蛋白受体（LDLR））、免疫系统功能（Toll样受体4（TLR4）、2'-5'-寡腺苷酸合成酶1（OAS1））和DNA修复（连接酶1（LIG1））的基因的多态性相关。
