ABSTRACT
This review aimed to summarize the pharmacogenetic studies of the most commonly used drugs in the chemotherapy of gastrointestinal (GI) tumors: oxaliplatin, irinotecan, and fluoropyrimidines. So far, it has not been possible to develop an effective genotype-based approach for oxaliplatin. More and more evidence is emerging in favor of the fact that the choice of a dose of fluorouracil based on pharmacogenetic testing according to DPYD*2A, can be not only effective but also cost-effective. Additional, well-planned trials of the UGT1A1 genotype-based approach to irinotecan therapy are predicted to reduce adverse drug events in people with the UGT1A1*28/*28 genotypes and improve treatment efficacy in the rest of the patients, which might be cost-effective.
Subject(s)
Gastrointestinal Neoplasms , Fluorouracil/adverse effects , Gastrointestinal Neoplasms/chemically induced , Gastrointestinal Neoplasms/drug therapy , Gastrointestinal Neoplasms/genetics , Genotype , Humans , Irinotecan/therapeutic use , Oxaliplatin/therapeutic useABSTRACT
This review aimed to summarize the pharmacogenetic studies of the most commonly used drugs in the chemotherapy of gastrointestinal (GI) tumors: oxaliplatin, irinotecan, and fluoropyrimidines. So far, it has not been possible to develop an effective genotype-based approach for oxaliplatin. More and more evidence is emerging in favor of the fact that the choice of a dose of fluorouracil based on pharmacogenetic testing according to DPYD*2A, can be not only effective but also cost-effective. Additional, well-planned trials of the UGT1A1 genotype-based approach to irinotecan therapy are predicted to reduce adverse drug events in people with the UGT1A1*28/*28 genotypes and improve treatment efficacy in the rest of the patients, which might be cost-effective.
ABSTRACT
This systematic review reflects the results of pharmacogenetic studies in the Russian Federation aimed at studying the genes involved in the drug biotransformation system. The works of Russian researchers found by us are mostly devoted to microsomal liver oxidation enzymes (metabolism) and membrane transporter systems (absorption and excretion). This review presents population-ethnic and associative clinical studies on the genes of the CYP450 system, noncytochrome oxidation enzymes (SULT1A1, CES1), membrane transporter system genes (ABCB1, SLCO1B1) and warfarin biotransformation enzymes (VKORC1, GGCX). The information is structured in the form of 11 tables, divided by regions of the Russian Federation.
Subject(s)
Cytochrome P-450 Enzyme System/genetics , Inactivation, Metabolic/genetics , Pharmacogenetics/trends , Alleles , Anticoagulants/adverse effects , Anticoagulants/therapeutic use , Genotype , Humans , Russia/epidemiology , Warfarin/adverse effects , Warfarin/therapeutic useABSTRACT
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/epidemiologySubject(s)
Acute Coronary Syndrome/genetics , Cytochrome P-450 CYP2C19/genetics , Cytochrome P-450 CYP3A/genetics , Cytochrome P450 Family 4/genetics , Polymorphism, Genetic/genetics , ATP Binding Cassette Transporter, Subfamily B/blood , ATP Binding Cassette Transporter, Subfamily B/genetics , Acute Coronary Syndrome/blood , Acute Coronary Syndrome/drug therapy , Blood Platelets/drug effects , Blood Platelets/metabolism , Clopidogrel/chemistry , Clopidogrel/metabolism , Clopidogrel/pharmacokinetics , Cytochrome P-450 CYP2C19/blood , Cytochrome P-450 CYP3A/blood , Cytochrome P450 Family 4/blood , Dose-Response Relationship, Drug , Female , Genotype , Humans , Male , Middle Aged , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/pharmacologyABSTRACT
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.
