Role of the genes of the natriuretic peptide and antioxidant defense systems in creating the risk of myocardial infarction development (the preliminary results of a pilot study)

M. Khutornaya, O. Khryachkova, A. Sinitskaya, A.O. Poddubnya, A. Ponasenko, V. Kashtalap
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Abstract

Aim: to reveal a relationship of single-nucleotide polymorphic variants of the genes of the natriuretic peptides, antioxidant defense systems and the endothelial function with the development of myocardial infarction. Patients and Methods: the study included 146 patients with myocardial infarction (MI) and maintained or moderately decreased left ventricular ejection fraction: 108 males and 38 females with a mean age of 57 (51; 64) years. The control group was composed of Kemerovo city residents without acute MI (n=300, 190 females and 110 males). To make the evaluation, genomic DNA was isolated from the peripheral blood by phenol- chloroform extraction according to the standard protocol. Real-time PCR method was used for genotyping. To conduct the study, 24 polymorphic variants of 14 genes (those of the natriuretic peptides, antioxidant defense systems and the endothelial function) were selected. Results: significant associations with the allelic variants of CBR1 and CBR3 genes (carbonyl reductase 1 and 3 genes) of the antioxidant defense system were found in the sample of studied patients with MI (not divided by gender or age). When the patients were divided by gender, the following associations were found: in males the single-nucleotide polymorphic variant (SNPV) genotypes CBR1 rs9024 and CBR3 rs1056892 had the protective effect against susceptibility to myocardial infarction (dominant inheritance pattern). It was demonstrated that allelic variants in the NPR2 gene (the gene of atrial natriuretic peptide receptor 2) comprised a risk factor for MI development. In females, a relationship between the assessed genetic factors and the MI development (dominant inheritance pattern) could be associated with SNPV genotypes NPR2 rs13288085 and rs7034957, CBR1 rs9024, and CBR3 rs1056892 which are characterized by the protective effect. Conclusion: some polymorphic variants of the genes of the natriuretic peptide and antioxidant defense systems are associated with the risk and the protective effect against MI susceptibility. The preliminary findings indicate that it is necessary to continue investigations of the identified single-nucleotide polymorphic variants and to assess their impact on the MI severity and the risk of recurrent cardiovascular events in the long-term perspective. KEYWORDS: myocardial infarction, gene, natriuretic peptides, antioxidant defense, polymorphic variants. FOR CITATION: Khutornaya M.V., Khryachkova O.N., Sinitskaya A.V. et al. Role of the genes of the natriuretic peptide and antioxidant defense systems in creating the risk of myocardial infarction development (the preliminary results of a pilot study). Russian Medical Inquiry. 2023;7(1):5–12 (in Russ.). DOI: 10.32364/2587-6821-2023-7-1-5-12.
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利钠肽基因和抗氧化防御系统在造成心肌梗死发展风险中的作用(初步研究的初步结果)
目的:探讨利钠肽基因单核苷酸多态性变异、抗氧化防御系统和内皮功能与心肌梗死发生发展的关系。患者和方法:该研究纳入146例心肌梗死(MI)患者,左室射血分数维持或中度降低:男性108例,女性38例,平均年龄57岁(51岁;64)年。对照组为无急性心肌梗死的克麦罗沃市居民300人,其中女性190人,男性110人。为了进行评价,根据标准方案,采用苯酚-氯仿萃取法从外周血中分离基因组DNA。采用实时荧光定量PCR法进行基因分型。为了进行研究,我们选择了14个基因(利钠肽、抗氧化防御系统和内皮功能基因)的24个多态性变异。结果:在研究的心肌梗死患者样本中发现与抗氧化防御系统CBR1和CBR3基因(羰基还原酶1和3基因)的等位基因变异有显著关联(未按性别或年龄划分)。当患者按性别划分时,发现以下关联:在男性中,单核苷酸多态性变异(SNPV)基因型CBR1 rs9024和CBR3 rs1056892对心肌梗死易感性具有保护作用(显性遗传模式)。研究表明,NPR2基因(心房利钠肽受体2基因)的等位基因变异是心肌梗死发生的一个危险因素。在女性中,被评估的遗传因素与MI发育(显性遗传模式)之间的关系可能与SNPV基因型NPR2 rs13288085和rs7034957、CBR1 rs9024和CBR3 rs1056892相关,这些基因型具有保护作用。结论:利钠肽和抗氧化防御系统基因的一些多态性变异与心肌梗死易感性的风险和保护作用有关。初步研究结果表明,有必要继续研究已确定的单核苷酸多态性变异,并从长远角度评估其对心肌梗死严重程度和心血管事件复发风险的影响。关键词:心肌梗死,基因,利钠肽,抗氧化防御,多态变异。引证:Khutornaya M.V, Khryachkova O.N, Sinitskaya A.V.等。利钠肽基因和抗氧化防御系统在造成心肌梗死发展风险中的作用(初步研究的初步结果)。俄罗斯医学调查。2023;7(1):5-12(俄文)。DOI: 10.32364 / 2587-6821-2023-7-1-5-12。
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