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Variability of CYP2C8 Polymorphisms in Three Jordanian Populations: Circassians, Chechens and Jordanian-Arabs

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Abstract

CYP2C8 is a member of Cytochrome P450 enzymes system. It plays an important role in metabolizing a wide range of exogenous and endogenous compounds. CYP2C8 is involved in the metabolism of more than 100 drugs, typical substrates include: anticancer agents, antidiabetic agents, antimalarial agents, lipid lowering drugs and many others that constitute 20% of clinically prescribed drugs. Genetic variations of CYP2C8 have been reported with different frequencies in different populations. These genetic polymorphisms can lead to differences in the efficacy and safety of different types of medications metabolized by CYP2C8. The aim of this study was to investigate the allele frequencies of CYP2C8*3 (rs10509681 and rs11572080) and CYP2C8*4 (rs1058930) polymorphisms in three populations living in Jordan; Circassians and Chechens and Jordanian-Arabs and compare those frequencies with other populations. A total of 200 healthy Jordanians, 93 Circassians and 88 Chechens were included in this study. Genotyping of CYP2C8*3 and CYP2C8*4 polymorphisms was done by using polymerase chain reaction (PCR) followed by Restriction Fragment Length Polymorphism (RFLP). Using the Chi-square test, we found that the prevalence of CYP2C8*3 and *4 among the three populations were significantly different. Moreover, the mutant allele CYP2C8*3 (416A) was only detected in the Jordanian-Arab population with an allele frequency of 0.082, while the mutant allele CYP2C8*4 (792G) was detected with frequencies of 0.065, 0.122, 0.017 in Jordanian-Arabs, Circassians and Chechens, respectively. As our results show, CYP2C8*3 was undetectable in our Circassians and Chechens samples, on the other hand, Circassians had the highest allele frequency of CYP2C8*4 compared to Chechens and Jordanian-Arabs. These genetic variations of the gene encoding the CYP2C8 drug metabolizing enzymes can lead to clinical differences in drug metabolism and ultimately variations in drug effectiveness and toxicities. This study provides evidence for the importance of personalized medicine in these populations and can be the foundation for future clinical studies.

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Acknowledgements

This study was supported by the University of Jordan in Amman and the Hashemite University in Zarqa, Jordan. Finally, the authors appreciative and acknowledge the support of Circassians and Chechens by their partnership on this study.

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Authors and Affiliations

  1. Department of Biopharmaceutics and Clinical Pharmacy, School of Pharmacy, University of Jordan, Amman, Jordan

    Sara Abudahab & Nancy Hakooz

  2. Department of Pharmacotherapy and Outcomes Science, School of Pharmacy, Virginia Commonwealth University, Richmond, VA, USA

    Sara Abudahab

  3. Department of Biology and Biotechnology, Hashemite University, Zarqa, Jordan

    Nuha Tobeh & Rana Dajani

  4. Department of Pharmacology, School of Medicine, University of Jordan, Amman, Jordan

    Esraa Gogazeh, Munir Gharaibeh & Malek Zihlif

  5. Department of Applied Biological Sciences, Jordan University of Science and Technology, Irbid, Jordan

    Laith Al-Eitan

  6. Department of Biotechnology and Genetic Engineering, Jordan University of Science and Technology, Irbid, Jordan

    Laith Al-Eitan

  7. University of Richmond, Richmond, VA, USA

    Rana Dajani

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  1. Sara Abudahab
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Correspondence to Nancy Hakooz.

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Abudahab, S., Hakooz, N., Tobeh, N. et al. Variability of CYP2C8 Polymorphisms in Three Jordanian Populations: Circassians, Chechens and Jordanian-Arabs. J Immigrant Minority Health 24, 1167–1176 (2022). https://doi.org/10.1007/s10903-021-01264-x

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