Genetic Polymorphisms Association in Restenosis of Coronary Arteries

Dana Taizhanova; Roza Bodaubay; Aliya Toleuova; Akerke Kalimbetova; Dmitriy Babenko; Anar Turmukhambetova; Ludmila  Akhmaltdinova; Olga Visternichan

doi:10.3889/oamjms.2020.4505

Authors

Dana Taizhanova Department of Internal Diseases, NCJSC “Medical University of Karaganda,” Karaganda, Kazakhstan https://orcid.org/0000-0001-6971-8764
Roza Bodaubay Scientific and Research Center (SRC), NCJSC “Medical University of Karaganda”, Karaganda, Kazakhstan https://orcid.org/0000-0001-5278-5477
Aliya Toleuova Department of Internal Diseases, NCJSC “Medical University of Karaganda,” Karaganda, Kazakhstan
Akerke Kalimbetova Scientific and Research Center (SRC), NCJSC “Medical University of Karaganda”, Karaganda, Kazakhstan https://orcid.org/0000-0003-1550-5469
Dmitriy Babenko Scientific and Research Center (SRC), NCJSC “Medical University of Karaganda”, Karaganda, Kazakhstan https://orcid.org/0000-0003-2280-2146
Anar Turmukhambetova Scientific and Research Center (SRC), NCJSC “Medical University of Karaganda”, Karaganda, Kazakhstan https://orcid.org/0000-0002-4668-3295
Ludmila Akhmaltdinova Scientific and Research Center (SRC), NCJSC “Medical University of Karaganda”, Karaganda, Kazakhstan
Olga Visternichan Department of Internal Diseases, NCJSC “Medical University of Karaganda,” Karaganda, Kazakhstan https://orcid.org/0000-0001-5433-264X

DOI:

https://doi.org/10.3889/oamjms.2020.4505

Keywords:

Gene polymorphism, Coronary heart disease, Percutaneous coronary angioplasty, Stenting, Restenosis, Clopidogrel, Acute coronary syndrome

Abstract

BACKGROUND: There is a reason to believe that the polymorphism of genes encoding some enzymes and receptors plays a role in increasing of restenosis development risk. It is common knowledge that ethnicity affects the frequency of heterozygous genotypes occurrence. There is the evidence that polymorphism of the FGB gene (rs1800790) and THBD gene was determined in the ethnic group of Kazakhs with restenosis of the coronary arteries, which can be considered as genetic predictors of restenosis development. Today, the questions of the role of the genetic component in the development of coronary heart disease (CHD) remain open.

AIM: Evaluation of gene polymorphism in patients with restenosis of coronary arteries after stent installation.

MATERIALS AND METHODS: The group consisted of Kazakh population of the age category from 45 to 65 years of both sexes: Group I (50 persons) patients with a diagnosis of CHD, with a fixed stent and the development of restenosis during the year; Group 2 (58 persons) – with a fixed stent and no restenosis during the year. The association of genetic polymorphisms was evaluated in accordance with the case–control design based on the generalized linear model assuming a log-additive inheritance model.

RESULTS: Thus, when comparing two groups using five patterns of inheritance, the following SNP were revealed: Codominant inheritance pattern – rs1045642 (p = 0.0427), dominant inheritance pattern – rs12041331 (p = 0.036088), rs13431554 (p = 0.025461), and rs1045642 (p = 0.012774), and overdominant inheritance pattern – rs12041331 (p = 0.051736), rs5918 (p = 0.057652), and rs13431554 (р = 0.036006). Thus, three SNPs associated with stenting were identified: rs7543130 (p = 0.009324), rs6785930 (p = 0.016858), and rs7819412 (p = 0.061325) and two SNPs associated with the development of restenosis after stent placement: rs1061781 (p = 0.063184) and rs342293 (p = 0.061636).

CONCLUSION: The polymorphisms associated with the risk of developing restenosis after stenting were determined: Codominant inheritance pattern – one polymorphism (rs1045642, p = 0.0427); dominant inheritance pattern – three polymorphisms (rs12041331, p = 0.036088; rs13431554, p = 0.025461; rs1045642, p = 0.012774), and overdominant inheritance pattern – one polymorphism (rs13431554, p = 0.036006). Based on the hybrid machine learning approach (RuleFit), four rules were obtained for assessing the empirical risk of restenosis developing after stenting – from 20% to 40%.

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