ABSTRACT
CYP2D6 and CYP2C19 are enzymes of essential significance for the pharmacokinetics of a multitude of commonly used antidepressants, antipsychotics, antiemetics, ß-blockers, opioids, antiestrogen, antacids, etc. Polymorphisms in the respective genes are well established as resulting in functional differences, which in turn can impact safety and efficacy. Importantly, the prevalence of genetic CYP2D6 and CYP2C19 variability differs drastically between populations. Drawing on the limited information concerning genotype frequencies in Bulgaria, we here analyzed 742 Bulgarian psychiatric patients predominantly diagnosed with depression and/or anxiety. Specifically, we analyzed frequencies of CYPC19*2, *4 and *17, as well as of CYP2D6*2, *3, *4, *5, *6, *10 and *41. In total, 571 out of 742 patients (77%) carried at least one variant which impacts metabolizer status. Overall, 48.6% of the studied individuals were classified as non-normal metabolizers of CYP2D6 with most exhibiting reduced function (38.2% intermediate metabolizers and 6.6% poor metabolizers). In contrast, for CYP2C19, the majority of non-normal metabolizers showed increased functionality (28.9% rapid and 5.5% ultrarapid metabolizers), while reduced activity metabolizer status accounted for 25.6% (23.8% intermediate and 1.8% poor metabolizers). These results provide an important resource to assess the genetically encoded functional variability of CYP2D6 and CYP2C19 which may have significant implications for precision medicine in Bulgarian psychiatry practice.
ABSTRACT
INTRODUCTION: Pharmacogenetics in psychiatry is currently gaining momentum. The efficiency of antipsychotic therapy is often limited by the lack of response and the presence of side effects. Pharmacogenetic variation is probably one of the causative factors for the observed interindividual differences in the response to and the side effects of antipsychotics, which could be addressed and whose negative effects could be avoided or mitigated. AIM: The present study aimed to conduct a comprehensive analysis of the frequency of DRD2 rs1799732, COMT rs4680, MC4R rs489693, and HTR2C rs3813929 in Bulgarian psychiatric patients. MATERIALS AND METHODS: The frequency of genotypes and the alleles of variants DRD2 rs1799732, COMT rs4680, MC4R rs489693, and HTR2C rs3813929 were studied in a cohort of 515 Bulgarian psychiatric patients using the polymerase chain reaction (PCR) method. RESULTS: We found no significant difference between our cohort and the dataset of the 1000 Genomes Project. Moreover, we found that 433 out of 515 patients carried at least one, and 191 out of 515 carried at least two variants which, based on multiple scientific sources with consistent findings, could potentially alter the expected response rate, time to respond and/or risk of side effects to antipsychotic medications. CONCLUSIONS: Considering the consistent data about the frequency of these pharmacogenetic variants, testing these genetic variants may prove useful in clinical practice. Further studies regarding the clinical interpretation and frequency distribution in larger cohorts and different populations are warranted.
