ABSTRACT
Background: The aim of this study was to determine the prevalence of CYP2C9, VKORC1, CYP2C19, ABCB1, CYP2D6 and SLCO1B1 genes polymorphisms among residents of the Volga region (Chuvash and Mari) and northern Caucasus (Kabardins and Ossetians). Materials & methods: The study involved 845 apparently healthy volunteers of both sexes of the four different ethnic groups living in the Russian Federation: 238 from the Chuvash ethnic group, 206 Mari, 157 Kabardins and 244 Ossetians. Results: Significant differences were identified in allele frequency of CYP2C9, VKORC1, CYP2C19, ABCB1, CYP2D6 and SLCO1B1 genes polymorphisms between the Chuvash and Kabardins, Chuvash and Ossetians, Mari and Kabardians, Mari and Ossetians.
Subject(s)
Biomarkers/metabolism , Cardiovascular Diseases/genetics , Cardiovascular System/metabolism , Ethnicity/genetics , Alleles , Cardiovascular Diseases/metabolism , Female , Gene Frequency/genetics , Humans , Male , Pharmacogenetics/methods , Pharmacogenomic Testing/methods , Polymorphism, Genetic/genetics , Prevalence , RussiaABSTRACT
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
BACKGROUND: Сytochrome P450 CYP2D6 activity affects antipsychotic therapy safety. 1846G>A (CYP2D6*4) polymorphism frequency varies among different ethnic groups. METHODS: We studied 1846G>A polymorphism in Tatar and Russian schizophrenic patients taking different antipsychotics and association of 1846G>A polymorphism and extrapyramidal disorders (EPD) frequency in schizophrenic patients on haloperidol monotherapy in daily doses up to 20 mg. RESULTS: Heterozygous 1846GA genotype frequency among Tatars was lower (23.8% vs. 32.4% in Russians), but the differences did not reach statistical significance. The 1846A allele frequency among Tatars was also lower (11.9% vs. 24.3% in Russians), but the difference was not quite significant (p=0.0592). Average daily haloperidol dose in the group without EPD was significantly higher than in the group with EPD (11.35±4.6 vs. 13.87±3.3 mg, p=0.0252), but average daily haloperidol dose/weight ratios in the compared groups had no significant differences. A statistically significant association between EPD development and heterozygous 1846GA genotype and 1846A allele carrier frequency was revealed among all schizophrenic patients and among those of Tatars. CONCLUSIONS: Further well-designed pharmacogenetic studies in different Russian regions are needed to improve psychotropic therapy safety and to establish evidence-based indications for pharmacogenetic testing in clinical practice.
