Gene Frequency of CYP2D6*4 and *10 Variants in Karachi Population
Background: CYP2D6 is to be considered the most pronounced gene in pharmacegenetic field which is involved in metabolizing ~25% of all clinically used neuroleptic drugs and other antidepressants. We designed a study to evaluate differential expression of CYP2D6*4 and CYP2D6*10 variants which are very prevalent in Asian countries and exhibit variation in drug metabolizing ability that affect therapeutic responses. Objective: The purpose of this study is to determine the genotypic frequencies of CYP2D6 *1 (normal metabolizer), *4 (poor metabolizer) and *10 (intermediate metabolizer) variants among schizophrenic subjects and compared with control group from a sub-set of Karachi population. Method: Genomic deoxyribonucleic acid (DNA ) was extracted and amplified with CYP2D6*4 and *10 primers using polymerase chain reaction (PCR) and digested by Bacillus stereothermophilus (BstN1) and Hemophilus parahemolyticus (Hph1) restriction enzymes. The digested bands were identified as wild type or mutants and their genotypic frequencies were estimated statistically by Hardy-Weinberg equation (HWE) and analyzed further under non-parametric Chi-square test. Results: The results mentioned the frequencies of CYP2D6*1 wild allele (57%) which produces functional enzyme in normal subjects but CYP2D6*4 variant (9%) that produces non-functional enzyme and CYP2D6*10 allele (70%) produces altered enzyme with reduced activity that was most prevalent in schizophrenic patients. Conclusion : Genotyping of CYP2D6 alleles among schizophrenic patients indicated prevalence of *4 and *10 variants in Karachi population producing non-functional and reduced functional drugs metabolizing enzymes respectively that increases the incurability rate of schizophrenia. Therefore, CYP2D6 gene screening program should be conducted routinely in clinical practice to help clinicians to prescribing appropriate doses according to patient’s genotype and minimize the sufferings of schizophrenia. Discussion: In last, drug response is a complex phenomenon that is dependent on genetic and environmental factors. CYP2D6 polymorphism may un-cured the schizophrenia due to improper drug metabolism and protein-proteins interaction that may alter the antipsychotic drugs metabolism among patients with variable drug resposes. Gene testing system need to establish for analyzing maximum patient’s genotypes predicted with poor metabolizer, intermediate metabolizer and ultrarapid metabolizer for the adjustment of antipsychotic drugs.