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      Identification of CYP2D6 allelic mutations in a sub-set of Karachi population

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      CYP2D6 alleles; Polymorphism; Depression; Drug metabolism; Karachi population.

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          Summary

          CYP2D6 is an enzyme family which is found in the liver and responsible to metabolize/digest antidepressants drugs and producing drug response. It has been found that changes in CYP2D6 gene produce different forms of enzymes which do not produce therapeutic effect in depressed patients because they unable to metabolize drugs properly and uncured the disease as a result they bear mental issues and unhealthy life. We designed a study to evaluate the CYP2D6 gene which is very prevalent in Asian countries including Pakistan and show improper drug digestion ability that affect therapeutic responses. We determined CYP2D6 gene polymorphism in depressed patients and compared them with normal people from a sub-set of Karachi population. For conducting this research DNA was separated from patient’s blood and run on PCR machine to visualize the CYP2D6 gene changes between depressed patients and normal people. Results were meaningful and clearly showed the differences between patients and normal with respect to antidepressants drugs responding ability and indicating why patients poorly respond drugs and suffering from depression. Because drug metabolism or drug digestion is a complex phenomenon that is dependent on genetic and environmental factors. CYP2D6 gene changes may alter the antidepressants drugs metabolism. Therefore, gene testing system need to be established that may help doctors for analyzing maximum patient’s gene profile and to prescribe right amount of antidepressants drugs dosage for minimizing the rate of depression.

          Abstract

          CYP2D6 gene polymorphism is considered a main obstacle in the process of drug metabolism under clinical diseases that affect pharmacokinetics of ~25% of antidepressants and other drugs. Inter-individual variation occurs in the amount and functional activity of CYP2D6 enzyme produce undesirable side effects. The primary aim of current research is to evaluate gene and genotypic frequencies of CYP2D6 *1 extensive metabolizer, *4 poor metabolizer and *10 intermediate metabolizer allelic variants among depressed patients and compared with normal subjects and other populations. Human genomic DNA was isolated. Genotyping was performed by Polymerase chain reaction followed by restriction endonucleases digestion for variants analysis. The results indicated gene frequency of CYP2D6*1 was 59% (CI 49.6,68.3%) in normal subjects whereas, CYP2D6*4 was 13% (CI 3.7, 22.3%) and CYP2D6*10 was 54% (44.7, 63.3%) predominantly found in depressed patients. The results demonstrate pronounced association of CYP2D6 *4 and *10 allelic variants with patient’s drug response activity.

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          Author and article information

          Journal
          ScienceOpen Preprints
          ScienceOpen
          25 March 2021
          Affiliations
          [1 ] Dr. Panjwani Center for Molecular Medicine and Drug Research
          Article
          10.14293/S2199-1006.1.SOR-.PPV2GGJ.v1

          This work has been published open access under Creative Commons Attribution License CC BY 4.0 , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Conditions, terms of use and publishing policy can be found at www.scienceopen.com .

          All data generated or analysed during this study are included in this published article (and its supplementary information files).

          Life sciences

          CYP2D6 alleles; Polymorphism; Depression; Drug metabolism; Karachi population.

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