The Frequency of the Minor Polymorphisms in the CYP2C19, VEGFR-2 Genes, and Clinical Outcomes in Russian and Buryat Patients with Acute Coronary Syndrome.

Aim: To determine the differences in the frequencies of polymorphic variants at the rs4244285(*2), rs4986893 (*3), rs12248560 (*17), loci of the CYP2C19 gene, and the rs2305948 locus of the VEGFR-2 gene in patients receiving clopidogrel treatment as part of a 30-day clinical outcome trial in the Russian and Buryat regions of East Siberia. Methods: The study included 118 Russian (from Irkutsk) and 109 Buryat (from Ulan-Ude) patients with emergency admission for percutaneous coronary interventional treatment of acute coronary syndrome (ACS). The patients were stratified by the presence of the CYP2C19*2, CYP2C19*3, CYP2C19*17 alleles, and the VEGFR-2 rs2305948 allele. Safety and efficacy endpoints were analyzed 30 days following coronary stenting (CS). Results: There was no significant difference found in the Russian and Buryat patients in terms of the frequency of the CYP2C19*2 minor allele (10.2% in the Russian against 12.8% in the Buryat patients, odds ratio [OR] = 1.167, confidence interval [CI] 0.729-2.323). However, the frequency of the CYP2C19*3 allele was significantly higher in the Buryat patients than in the Russian patients (12.8% vs. 2.1%), OR = 5.600, CI 2.579-17.974; while in the Russian patients the frequency of the CYP2C19*17 allele was higher than the Buryat patients (23.3% in Russian patients vs. 10.1% in Buryat, OR = 2.500, CI 1.587-4.618). No significant differences were found in the prevalence of the VEGFR-2 rs2305948 alleles between the two groups of patient populations (12.5 in Buryat patients vs. 11.5% in Russian, OR = 1.040, CI 0.614-1.980). The Buryat patients were highly significantly more likely to experience adverse effects associated with the inefficacy of clopidogrel treatment, that is, early recurrent ischemic pains after CS, than the Russian patients (χ2 = 11.325, p < 0.001). Conclusion: The Buryat patients receiving clopidogrel treatment after CS have a reduced risk of small or large hemorrhages, and an increased risk of thrombotic complications compared with Caucasians. These results suggest that other antiplatelet drugs should be used for treating the Buryat patients with ACS.

CYP2C19 polymorphism frequency in Russian patients in Central Russia and Siberia with acute coronary syndrome.

PURPOSE: The aim of this study is to investigate the frequency of CYP2C19*2, *3 allelic variants, associated with poor response to clopidogrel, and CYP2C19*17, associated with excessive response to clopidogrel, in patients with acute coronary syndrome (ACS) from Siberia and Moscow regions of Russia. PATIENTS AND METHODS: The study included 512 ACS patients who were subsequently treated with coronary arterial stenting. The subjects assigned were from the cities of Central (Novosibirsk, Kemerovo), Eastern (Irkutsk), Northern (Surgut) Siberia regions and from Moscow region. The mean age of patients enrolled was 63.9±10.9 years. Among the assigned subjects, the proportion of men accounted for 80% and women 20%. RESULTS: According to the results obtained in the present study, from 16% up to 27.5% of patients in different regions of Russia have at least one CYP2C19 "poor metabolizer" (PM) allele variant affecting clopidogrel metabolism and, therefore, suppressing its antiplatelet activity. CYP2C19*17 allele variant was identified with the frequency of 15.4% up to 33.3%. The study revealed the presence of statistically significant differences in CYP2C19*3 allele frequency between the Russian ethnic group patients from Eastern and Central Siberia (p=0.001; odds ratio=1.05 [95% confidence interval 1.01-1.09]). CONCLUSION: The study revealed statistically significant differences between the allele frequencies in Eastern and Central Siberia, which can probably be caused by a considerable number of Buryats inhabiting Eastern Siberia.