The aim of this study is to assess the influence of gene CYP2C19, CYP3A4, CYP3A5 and ABCB1 polymorphisms on clopidogrel antiplatelet activity, rivaroxaban concentration equilibrium, and clinical outcomes among patients with acute coronary syndrome and non-valvular atrial fibrillation. Methods: In the multicenter prospective registry study of the efficacy and safety of a combined antithrombotic therapy 103 patients with non-valvular atrial fibrillation both undergoing or not a percutaneous coronary intervention were enrolled. The trial assessed the primary outcomes (major bleeding, in-hospital death, cardiovascular death, stroke\transient ischaemic attack, death/renal insufficiency) and secondary outcomes (platelet reactivity units (PRU), rivaroxaban concentration). Results: For none of the clinical outcomes when combined with other covariates, the carriership of polymorphisms CYP3A5*3 rs776746, CYP2C19*2 rs4244285;*17 rs12248560, ABCB1 3435 C>T, ABCB1 rs4148738 was significant. None of the markers under study (CYP3A5*3 rs776746, CYP2C19*2 rs4244285, *17 rs12248560, ABCB1 3435 C>T, ABCB1 rs4148738) has proven to affect rivaroxaban equilibrium concentration in blood plasma among patients with atrial fibrillation and acute coronary syndrome. Conclusion: In situations of double or triple antithrombotic rivaroxaban and clopidogrel therapy among patients with atrial fibrillation and acute coronary syndrome, the genetic factors associated with bleeding complications risk (CYP2C19*17) may prove to be clinically relevant.

IntroductionProton pump inhibitors, which are widely used as acid-inhibitory agents for the treatment of peptic ulcers, are mainly metabolized by 2C19 isoenzyme of cytochrome P450 (CYP2C19). CYP2C19 has genetic polymorphisms, associated with extensive, poor, intermediate or ultra-rapid metabolism of proton pump inhibitors. Genetic polymorphisms of CYP2C19 could be of clinical concern in the treatment of peptic ulcers with proton pump inhibitors.AimTo investigate the frequencies of CYP2C19*2, CYP2C19*3, and CYP2C19*17 alleles and genotypes in Russian patients with peptic ulcers.MethodsWe retrospectively reviewed the cases of 971 patients of Caucasian origin with Russian nationality from Moscow region with endoscopically and histologically proven ulcers, 428 males (44%) and 543 females (56%). The mean age was 44.6±11.9 years (range: 15–88 years). DNA was extracted from ethylenediaminetetraacetic acid whole blood samples (10 mL). The polymorphisms CYP2C19 681G.A (CYP2C19*2, rs4244285), CYP2C19 636 G.A (CYP2C19*3, rs4986893) and CYP2C19 -806 C.T (CYP2C19*17, rs12248560) were evaluated using real-time polymerase chain reaction.ResultsRegarding CYP2C19 genotype, 317 patients (32.65%) out of 971 were CYP2C19*1/*1 carriers classified as extensive metabolizers. Three hundred and eighty-six (39.75%) with CYP2C19*1/*17 or CYP2C19*17/*17 genotype were ultra-rapid metabolizers. Two hundred and fifty-one people (25.85%) were intermediate metabolizers with CYP2C19*1/*2, CYP2C19*2/*17, CYP2C19*1/*3, CYP2C19*3/*17 genotypes. Seventeen patients (1.75%) with CYP2C19*2/*2, CYP2C19*3/*3, CYP2C19*2/*3 genotypes were poor metabolizers. The allele frequencies were the following: CYP2C19*2 – 0.140, CYP2C19*3 – 0.006, CYP2C19*17 – 0.274.ConclusionThere is a high frequency of CYP2C19 genotypes associated with modified response to proton pump inhibitors in Russian patients with peptic ulcers. Genotyping for CYP2C19 polymorphisms is suggested to be a useful tool for personalized dosing of proton pump inhibitors.

Проблема статин-индуцированной миопатии В настоящее время статины широко применяются в клинической практике для лечения гиперлипидемии, для первичной и вторичной профилактики сердечно-сосудистых событий, а также при остром коронарном синдроме (наибольшая доказательная база -макси-мально допустимые дозы). Доказательная база эф-фективности статинов при данных состояниях обшир-на. Однако в последнее время все большую актуальность приобретает проблема безопасности при применении статинов, в частности, со стороны поперечно-полоса-той мускулатуры. И если рабдомиолиз, как опасное для жизни осложнение со стороны поперечно-полосатой мускулатуры, при применении статинов встречается ред-ко (0,15 на 1 миллион назначений), то другие формы статин-индуцированной миопатии у пациентов, при-нимающих данные лекарственные средства (ЛС) [1], мо-гут встречаться часто. Предполагают, что механизмом развития данного осложнения терапии статинами мо-жет быть угнетение синтеза коэнзима Q (что приводит к нарушению в дыхательной цепи), а по некоторым дан-ным это может быть связано со снижением уровня ак-тивного метаболита витамина D [2]. При этом под ста-тин-индуцированной миопатией нужно понимать лю-бые мышечные симптомы или мышечную патологию, под миалгией -миопатию без повышения плазменной креатининсофокиназы (КФК), под миозитом -мио-патию с повышением КФК. И, наконец, рамбомиолиз -это миопатия с повышением КФК более чем в 10 раз The clinical significance of the SLCO1B1 gene polymorphism (encoding an organic anion transport polipeptide) in the development of statin induced myopathy is considered. Possible tactics of statin dose determination on the basis of pharmacogenetic testing is discussed. Indications for the use of this approach in clinical practice that should increase the efficacy and safety of the statin therapy are also considered.

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