PHARMACOGENETIC TESTING BY POLYMORPHIC MARKERS G1846A (CYP2D6*4) AND C100T (CYP2D6*10) CYP2D6 GENE IN CORONARY HEART DISEASEPATIENTS, TAKING BETA-BLOCKERS IN THE SAKHA REPUBLIC (YAKUTIA)

DOI: https://doi.org/10.29296/24999490-2018-04-09

K.B. Mirzaev(1), D.S. Fedorinov(1, 2), D.A. Sychev(1), N.R. Maksimova(3), Ya.V. Chertovskih(4), Ya.V. Popova(4), S. M. Tarabukina(3), Z.A. Rudykh(4) 1-Russian Medical Academy of Continuous Professional Education, Barrikadnaya str., 2/1, Moscow, 125993, Russian Federation; 2-I.M. Sechenov First Moscow State Medical University, Trubetskaya str., 8–2, Moscow, 119991, Russian Federation; 3-M.K. Ammosov North-Eastern Federal University, Kulakovskogo str., 42, Yakutsk, 677007, Russian Federation; 4-Republican Hospital №3, Gorky Str., 94, Yakutsk, 677027, Russian FederationE-mail: [email protected]

Introduction. The aim of this study to determine carrier frequencies of polymorphic markers G1846A (CYP2D6*4) and C100T (CYP2D6*10) of the CYP2D6 gene in coronary heart disease (CHD) patients in Russian and Yakut ethnic groups. The association between theadministration of higher doses of bisoprolol and metoprolol and the carriage of these polymorphic markers related to the decreased function of the haplotype of CYP2D6 was also studied. Materials and methods. The study included 201 CHD patients (aged 66±8,7years) receiving metoprolol in the titrated dose (12,5 – 150 mg), bisoprolol (2,5 – 10 mg) or atenolol (50 mg). 93 patients were Russians (30 men and 63 women) and 108 patients wereYakuts (54 men and 54 women). Genotyping of G1846A (CYP2D6*4) and C100T (CYP2D6*10) polymorphisms was performed by using polymerase real-time chain reaction. Results. The distribution of alleles and genotypes in both ethnic groups complies with Hardy – Weinberg Equilibrium (р>0,05). In genotyping CHD patients in the Russian and Yakut ethnic groups, there was no significant difference in the prevalence rate of polymorphic markers G1846A (10,8 vs 10,2; p=0,871) and C100T (16,1 vs 16,2; p=1). In patients carrying polymorphic marker G1846A the dose of bisoprololwas established to be lower than in the control group, p=0,0289. Conclusions. The frequency of carriage of polymorphic markers, which theoretically should differ between Russians and Yakuts as representatives of two different races, in practice turned out to be the same (1846A: 10,8 vs 10,2%; p=0,871; 100T: 16,1 vs 16,2%, p=1).
Keywords: 
CYP2D6*4, CYP2D6*10, metoprolol, bisoprolol, pharmacogenetics
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