Implications of genetic variation of common drug metabolizing enzymes and ABC transporters among the Pakistani population

Authors

Nasir Ali Afsar, Jinnah Medical and Dental College, Sohail University, Karachi, Pakistan
Henrike Bruckmueller, Institute of Experimental and Clinical Pharmacology, Christian Albrechts University Kiel, Hospitalstr. 4, Kiel, 24105, Germany
Anneke Nina Werk, Institute of Experimental and Clinical Pharmacology, Christian Albrechts University Kiel, Hospitalstr. 4, Kiel, 24105, Germany
Muhammad Kashif Nisa, Jinnah Medical and Dental College, Sohail University, Karachi, Pakistan
H R. Ahmad, Aga Khan UniversityFollow
Ingolf Cascorbi, Institute of Experimental and Clinical Pharmacology, Christian Albrechts University Kiel, Hospitalstr. 4, Kiel, 24105, Germany

Document Type

Article

Department

Biological and Biomedical Sciences

Abstract

Genetic polymorphism of drug metabolizing enzymes and transporters may influence drug response. The frequency varies substantially between ethnicities thus having implications on appropriate selection and dosage of various drugs in different populations. The distribution of genetic polymorphisms in healthy Pakistanis has so far not been described. In this study, 155 healthy adults (98 females) were included from all districts of Karachi. DNA was extracted from saliva and genotyped for relevant SNVs in CYP1A1, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4 and CYP3A5 as well as ALDH3A1, GSTA1, ABCB1 and ABCC2. About 64% of the participants were born to parents who were unrelated to each other. There was generally a higher prevalence (p < 0.05) of variant alleles of CYP450 1A2, 2B6, 2C19, 3A5, ALDH3A1, GSTM1 as well as ABCB1 and ABCC2 in this study cohort than in other ethnicities reported in the HapMap database. In contrast, the prevalence of variant alleles was lower in GSTA1. Therefore, in the Pakistani population sample from Karachi a significantly different prevalence of variant drug metabolizing enzymes and ABC transporters was observed as compared to other ethnicities, which could have putative clinical consequences on drug efficacy and safety.

Comments

Pagination are not provided by the author/publisher

Publication (Name of Journal)

Scientific Reports

Recommended Citation

Afsar, N. A., Bruckmueller, H., Werk, A. N., Nisa, M. K., Ahmad, H. R., Cascorbi, I. (2019). Implications of genetic variation of common drug metabolizing enzymes and ABC transporters among the Pakistani population. Scientific Reports, 9(1), 7323.
Available at: https://ecommons.aku.edu/pakistan_fhs_mc_bbs/752

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.