Association between genetic determinants of clopidogel metabolism and clinical cardiovascular risk indicators in Buryat patients

Abstract

Background. In some patients, the metabolism of clopidogrel is altered because of the presence of polymorphic variants rs4244285 (* 2), rs4986893 (* 3) and rs12248560 (* 17) in the CYP2C19 gene. There is also evidence of decreased efficacy of clopidogrel in individuals with the T/T genotype in the variant rs2305948 of the VEGFR-2 gene. Nevertheless, this medication is used widely in Russia due to the availability of generic anticoagulants.Aim. To assess the prevalence of the following polymorphic variants of CYP2C19: rs4244285 (* 2), rs4986893 (* 3) and rs12248560 (* 17); assess the prevalence of the rs2305948 variant of VEGFR-2, and determine cardiovascular risk factors in patients of Buryat nationality.Methods. The study included 113 patients of Buryat nationality who underwent coronary stent placement due to acute coronary syndrome. Patients were stratified by the presence of the following alleles: CYP2C19 * 2, *3, *17 and VEGFR-2 rs2305948. The following laboratory parameters were measured for all patients: blood glucose, lipid spectrum, creatinine, and glomerular filtration rate. The severity of coronary atherosclerosis was evaluated.Results. The frequencies of the alleles and halotypes (CYP2C19 * 2, * 3 and *17) were determined. An association between the carriage of the C/C genotype in rs2305948 and a <60 ml/min/1.73 m2 decrease in glomerular filtration rate (χ2 = 4.185, p = 0.032) were found. Additionally, the C/C genotype in rs2305948 was associated with higher blood pressure (χ2 = 12.593, p = 0.001). For men, we identified a positive correlation between the rs2305948 C/C allele and the number of significant coronary stenoses (R = 0.227, p < 0.05).Conclusion. Among Buryat patients with acute coronary syndrome and percutaneous coronary intervention, the CYP2C19*2,*3 polymorphic variants were associated with a 46.0% decrease in the metabolic rate for clopidogrel. Furthermore, we identified several associations between the C/C genotype in the rs2305948 variant of VEGFR-2 with a number of cardiovascular risk factors. Received 2 September 2019. Revised 24 October 2019. Accepted 30 October 2019. Funding: The study did not have sponsorship. Conflict of interest: Authors declare no conflict of interest. Author contributionsConception and study design: V.D. Altayev, K.V. Protasov, G.I. LifshitsData collection and analysis: Е.М. Zelenskaya, K.Y. Nikolaev, O.S. Donirova, V.D. Altayev, K.V. Protasov, E.N. Voronina, G.I. LifshitsDrafting the article: Е.М. ZelenskayaCritical revision of the article: Е.М. ZelenskayaFinal approval of the version to be published: Е.М. Zelenskaya, K.Y. Nikolaev, O.S. Donirova, V.D. Altayev, K.V. Protasov, E.N. Voronina, G.I. Lifshits