Inter-ethnic genetic variations and novel variant identification in the partial sequences of CYP2B6 gene in Pakistani population

Sagheer Ahmed; Hizbullah Khan; Asifullah Khan; Muhammad Hanif Bangash; Abrar Hussain; Mughal Qayum; Mohammad Hamid Hamdard

doi:10.7717/peerj.11149

Inter-ethnic genetic variations and novel variant identification in the partial sequences of CYP2B6 gene in Pakistani population

PeerJ. 2021 Jul 23:9:e11149. doi: 10.7717/peerj.11149. eCollection 2021.

Authors

Sagheer Ahmed¹, Hizbullah Khan¹, Asifullah Khan², Muhammad Hanif Bangash³, Abrar Hussain⁴, Mughal Qayum⁵, Mohammad Hamid Hamdard⁶

Affiliations

¹ Department of Basic Medical Sciences, Shifa College of Pharmaceutical Sciences, Shifa Tameer-e-Millat University, Islamabad, Pakistan.
² Department of Biochemistry, Abdul Wali Khan University, Mardan, Pakistan.
³ Pakistan Institute of Nuclear Science & Technology, Islamabad, Pakistan.
⁴ Baluchistan University of Information Technology and Management Sciences, Quetta, Pakistan.
⁵ Department of Pharmacy, Kohat University of Science & Technology, Kohat, Pakistan.
⁶ Faculty of Biology, Kabul University, Kabul, Afghanistan.

Abstract

Background: Some single nucleotide polymorphisms (SNPs) in the cytochrome P450 (CYP)2B6 gene lead to decreased enzyme activity and have an impact on drug metabolism. The present study was designed to investigate the patterns of genetic distinction across a hypervariable region of the CYP2B6 gene, known to contain important SNPs, i.e. rs4803419 and rs3745274, among five major ethnic groups of the Pakistani population.

Methods: Arlequin v3.5.DnaSPv6.12. and network 5 resources were used to analyze population genetic variance in the partial CYP2B6 gene sequences obtained from 104 human samples belonging to Punjabi, Pathan, Sindhi, Seraiki and Baloch ethnicities of Pakistan. The partial CYP2B6 gene region analyzed in the current study is previously known to possess important SNPs.

Results: The data analyses revealed that genetic variance among samples mainly came from differentiation within the ethnic groups. However, significant genetic variation was also found among the various ethnic groups. The high pairwise Fst genetic distinction was observed between Seraiki and Sindhi ethnic groups (Fst = 0.13392, P-value = 0.026) as well as between Seraiki and Balochi groups (Fst = 0.04303, P-value = -0.0030). However, the degree of genetic distinction was low between Pathan and Punjabi ethnic groups. Some SNPs, including rs3745274 and rs4803419, which are previously shown in strong association with increased plasma Efavirenz level, were found in high frequency. Besides, a novel SNP, which was not found in dbSNP and Ensemble databases, was identified in the Balochi ethnicity. This novel SNP is predicted to affect the CYP2B6 splicing pattern.

Conclusion: These results may have significant implications in Pakistani ethnicities in the context of drugs metabolized by CYP2B6, especially in Seraiki and Balochi ethnicity. The novel heterogeneous SNP, found in the present study, might lead to altered drug-metabolizing potential of CYP2B6 and, therefore, may be implicated in non-responder phenomenon.

Keywords: Balochi; CYP2B6; Pakistan; Pathan; Pharmacogenetics; Population genetics; Punjabi; Seraiki; Sindhi; Urdu.

Grants and funding

This work was supported by a research grant to Dr. Sagheer Ahmed by the Shifa Tameer-e-Millat University, Islamabad. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.