Key result
Buryat patients with ACS had a significantly higher frequency of the CYP2C19*3 allele compared to Russian patients (12.8% vs 2.1%; OR 5.600, 95% CI 2.579-17.974), increasing their risk of clopidogrel inefficacy.
Why the study?
Differences in CYP2C19 and VEGFR-2 polymorphic variant frequencies and associated 30-day clinical outcomes during clopidogrel therapy had not been compared between Russian and Buryat patients in East Siberia.
Does ethnicity (Buryat vs Russian) affect the frequency of CYP2C19 polymorphisms and clinical outcomes in ACS patients treated with clopidogrel?
Observational (n=227)
Yes
Does ethnicity (Buryat vs Russian) affect the frequency of CYP2C19 polymorphisms and clinical outcomes in ACS patients treated with clopidogrel?
Odds Ratio: 5.6 (95% CI 2.579–17.974)
Absolute Event Rate: 12.8% vs 2.1%
Buryat patients with ACS have a higher prevalence of the CYP2C19*3 loss-of-function allele and experience more ischemic events on clopidogrel compared to Russian patients, suggesting a need for alternative antiplatelet agents in this population.
May inform antiplatelet selection in Buryat ACS patients; leaves open prospective validation of genotyping-guided therapy.
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.
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Zelenskaya et al. (2020) conducted an observational in Acute coronary syndrome (n=227). Buryat ethnicity vs. Russian ethnicity was evaluated on CYP2C19*3 allele frequency (OR 5.600, 95% CI 2.579-17.974). Buryat patients with ACS had a significantly higher frequency of the CYP2C19*3 allele compared to Russian patients (12.8% vs 2.1%; OR 5.600, 95% CI 2.579-17.974), increasing their risk of clopidogrel inefficacy.
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