ABSTRACT
This study was aimed to investigate the prevalence of CYP2C9*2 (p.430C > T, rs1799853), CYP2C9*3 (p.1075A > C, rs1057910), CYP4F2*3 (p.1297G > A, rs2108622), CYP2C19*2 (p.681G > A, rs4244285), CYP2C19*3 (p.636G > A, rs4986893), CYP2C19*17 (p.1260C > A, rs12248560), ABCB1 (p.3435C > T, rs1045642), CYP2D6*4 (p.1846G > A, rs3892097), SLCO1B1*5 (p.521T > C, rs4149056) and CES1 (p.1168-33A > C, rs2244613) among Tatars and Balkars ethnic groups living in Russia to provide a basis for future clinical studies concerning on understanding of population-level differences in drug response. The study involved 341 apparently healthy, unrelated, and chronic medication-free volunteers of both sexes of ethnic groups of Tatars and Balkars living in Volga and Caucasus regions of Russia. Genotyping was performed using real-time polymerase chain reaction-based methods. The allelic prevalence of studied markers in ethnic groups were compared with Russians as a largest ethnic group in Russia. Statistically significant differences for the following gene polymorphisms were found between both ethnic groups in respect of different markers and with Russians. Our study shows differences in prevalence of the main relevant pharmacogenetic markers in Tatars and Balkars. These findings should be taken into consideration for personalization algorithms development and pharmacogenetics implementation in regions with ethnic minorities as Russia has.
Subject(s)
Biomarkers, Pharmacological/metabolism , Ethnicity/genetics , White People/genetics , ATP Binding Cassette Transporter, Subfamily B/genetics , Adult , Carboxylic Ester Hydrolases/genetics , Cytochrome P-450 CYP2C19/genetics , Cytochrome P-450 CYP2C9/genetics , Cytochrome P-450 CYP2D6/genetics , Cytochrome P450 Family 4/genetics , Female , Gene Frequency , Genotype , Humans , Liver-Specific Organic Anion Transporter 1/genetics , Male , Pharmacogenetics/methods , Polymorphism, Single Nucleotide , Russia/epidemiology , TranscriptomeABSTRACT
This study was aimed to investigate the prevalence of the CES1 gene (c.1168-33A > C, rs2244613) polymorphism among 12 different ethnic groups living in Russia to provide a basis for future clinical studies concerning genetic determinants of dabigatran safety. The study involved 1630 apparently healthy, unrelated, and chronic medication-free volunteers of both genders from 12 different ethnic groups in Russia: 136 Russians, 90 Avars, 50 Dargins, 46 Laks, 120 Kabardians, 112 Balkars, 244 Ossetians, 206 Mari, 204 Mordvinians, 238 Chuvashes, 114 Buryats and 70 Nanays. Genotyping was performed by using real-time polymerase chain reaction-based methods. The allelic prevalence of the ethnic groups was compared with Caucasus population participating in the RE-LY study. Statistically significant differences for the following gene polymorphism were found between all ethnic groups and RE-LY participants. Based on obtained results, it can be assumed that patients of all ethnic groups living in Russia taking dabigatran have a lower risk of bleeding.
Subject(s)
Carboxylic Ester Hydrolases/genetics , Alleles , Biomarkers, Pharmacological/blood , Carboxylic Ester Hydrolases/metabolism , Dabigatran/pharmacology , Dabigatran/therapeutic use , Ethnicity/genetics , Female , Gene Frequency/genetics , Genetics, Population , Genotype , Healthy Volunteers , Humans , Male , Pharmacogenetics/methods , Polymorphism, Single Nucleotide/genetics , Prospective Studies , Russia , White People/geneticsABSTRACT
BACKGROUND: The efficiency and safety of drug therapy depends on the peculiarities of functioning of the P450 cytochrome group and transporting proteins. There are significant differences for single-nucleotide polymorphism (SNP) frequency. MATERIALS AND METHODS: We studied the peculiarities of P450 cytochrome polymorphisms, SLCO1B1 transporting protein, and P-glycoprotein carriage in healthy volunteers in the Nanai ethnic group living in Russia, and compared them to the carriage of SNPs in the Russian population according to literature data. RESULTS: After performing the real-time polymerase chain reactions on the samples from 70 healthy volunteers from the Nanai group, for the CYP2C9*2C430T polymorphism we determined 70 CC-genotype carriers. As for the CYP2C9*3A1075C polymorphism, we found 62 AA-genotype carriers and eight AC-genotype carriers. For the CYP2C19*2G681A polymorphism, we determined 39 GG-genotype carriers and 28 GA-genotype carriers, for the CYP2C19*3G636A polymorphism 58 GG-genotype carriers and 12 GA-genotype carriers, and for the CYP2C19*17C806T polymorphism 67 CC-genotype carriers and three CT-genotype carriers. For the CYP2D6*4G1846A polymorphism, the GG genotype had 68 carriers, and the GA genotype two carriers. For the ABCB1*6C3435T polymorphism, there were 19 CC-genotype carriers and 39 CT-genotype carriers. For the SLCO1B1*5T521C polymorphism, the TT genotype had 41 carriers and the CT genotype 25 carriers. The distribution of genotypes fitted the Hardy-Weinberg equilibrium for all the polymorphisms, except those of CYP2C9*2. There were also significant differences in allele frequencies for some polymorphisms between the Nanais and the Russians. CONCLUSION: In the Nanai population, there are polymorphisms connected with the decrease in safety and efficiency of drug therapy. Studying the ethnic differences might influence the determination of priority in the introduction of pharmacogenetic tests in clinical practice in different regions of Russia.
