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1.
Drug Metab Pers Ther ; 33(4): 195-200, 2018 12 19.
Article in English | MEDLINE | ID: mdl-30325731

ABSTRACT

Background The aim of this study was to determine carrier frequencies of the 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 the administration 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. Methods The study included 201 CHD patients (aged 66±8.7 years) receiving metoprolol in titrated dose (12.5-150 mg), bisoprolol (2.5-10 mg) or atenolol (50 mg). Ninety-three patients were Russian (30 men and 63 women), and 108 patients were Yakut (54 men and 54 women). Results In genotyping CHD patients in the Russian and Yakut ethnic groups, there was no significant difference in the prevalence rate of the polymorphic markers G1846A (10.8 vs. 10.2; p=0.871) and C100T (16.1 vs. 16.2; p=1). In patients carrying the polymorphic marker G1846A, the dose of bisoprolol was established to be lower than that in the control group (p=0.0289). Conclusions The carriage frequency 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.


Subject(s)
Adrenergic beta-Antagonists/therapeutic use , Coronary Disease/drug therapy , Cytochrome P-450 CYP2D6/genetics , Polymorphism, Single Nucleotide , Adrenergic beta-Antagonists/blood , Aged , Coronary Disease/blood , Coronary Disease/epidemiology , Coronary Disease/genetics , Dose-Response Relationship, Drug , Gene Frequency , Humans , Male , Middle Aged , Pharmacogenomic Testing , Russia/epidemiology
2.
Drug Metab Pers Ther ; 33(2): 91-98, 2018 Jun 27.
Article in English | MEDLINE | ID: mdl-29738309

ABSTRACT

BACKGROUND: The focus of the study is to determine the prevalence of CYP2C19 alleles, associated with the risk of changes in the pharmacological response to clopidogrel and proton pump inhibitors in patients with acute coronary syndrome (ACS) and gastric ulcer from Russian and Yakut ethnic groups. METHODS: The research included 411 patients with ACS (143 Russians and 268 Yakuts) and 204 patients with histologically confirmed gastric ulcer (63 Russians and 141 Yakuts). Genotyping of 681G>A and 636G>A polymorphisms was performed by using polymerase real-time chain reaction. RESULTS: In both ethnic groups, Hardy-Weinberg equilibrium was followed in a distribution of alleles and genotypes in the population (p>0.05). The 681A allele frequency in the Yakut ethnic group was higher than in the Russian group: 17.53% vs. 8.39% (p=0.001). No statistically significant difference was found in the frequency of 636A in Yakuts and Russians with ACS: 3.92% vs. 3.50% (p=0.840). While comparing the frequency distribution of alleles 681A (13.49% vs. 14.54%, p=0.878) and 636A (7.94% vs. 7.80%, p=1) in patients with a gastric ulcer from Russian and Yakut ethnic groups, no significant difference was found in carrier frequency. CONCLUSIONS: The results of the present study may be helpful for developing guidelines for CYPC19 genotype-directed antiplatelet therapy for Yakut and Russian patients.


Subject(s)
Acute Coronary Syndrome/drug therapy , Clopidogrel/therapeutic use , Cytochrome P-450 CYP2C19/genetics , Pharmacogenomic Testing/methods , Pharmacogenomic Variants , Platelet Aggregation Inhibitors/therapeutic use , Polymorphism, Single Nucleotide , Proton Pump Inhibitors/therapeutic use , Stomach Ulcer/drug therapy , Acute Coronary Syndrome/enzymology , Acute Coronary Syndrome/ethnology , Acute Coronary Syndrome/genetics , Aged , Clinical Decision-Making , Clopidogrel/pharmacokinetics , Cytochrome P-450 CYP2C19/metabolism , Female , Gene Frequency , Genotype , Humans , Male , Middle Aged , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation Inhibitors/pharmacokinetics , Precision Medicine , Predictive Value of Tests , Proton Pump Inhibitors/adverse effects , Proton Pump Inhibitors/pharmacokinetics , Siberia/epidemiology , Stomach Ulcer/enzymology , Stomach Ulcer/ethnology , Stomach Ulcer/genetics
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