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Genome-wide screening of pharmacogenomic biomarkers in jordanian patients with genetic disorders

The Pharmacogenomics Journal volume 25, Article number: 28 (2025) Cite this article

Subjects

Abstract

Introduction

Pharmacogenomics (PGx) testing aims to identify the most appropriate drug and dose for individual patients based on their genetic profiles. In Jordan, patients with genetic disorders often use multiple medications, some of which have clinical guidelines recommending PGx testing.

Aim

This study aimed to screen the frequency of clinically relevant PGx biomarkers among a sample of Jordanian patients with genetic disorders.

Methods

A total of 76 patients (average age 13 ± 14 years; 71% under 13 years old) attending INNOVIA Biobank in Amman between January 2023 and January 2024 participated. Buccal swabs were collected, and DNA was extracted for whole-genome sequencing using Illumina technology. Variant calling and annotation were performed using DRAGEN, Geneyx, and ANNOVAR tools. A PGx panel based on PharmCAT v2.8.3 and Clinical Pharmacogenetics Implementation Consortium v1.30.0, covering 20 pharmacogenes, was applied.

Result

In Phase I enzymes, CYP2D6*10 (13.2%) and CYP2C19*1/*17 (18.4%) were most common, while CYP2C9 and CYP3A4 variants were less frequent. In Phase II enzymes, UGT1A180 + 2B appeared in 7.9% and multiple DPYD variants found in heterozygous forms 925%). Among toxicity-related markers, G6PD and HLA-B*57:01 were detected in 3.9 and 2.6%, respectively. Transporter gene variants in SLCO1B1 (15%) and ABCB1 (21.1%) were relatively frequent. For pharmacodynamic genes, VKORC1 −1639G > A (52.6%) and CYP4F2 V433M (40.8%) were most prevalent. Accordingly, over half of the patients had genetic variants affecting warfarin response, with additional impacts seen on antidepressants (45%), clopidogrel (35%), and anticancers (30%). Conclusions, this study demonstrates the presence of key PGx biomarkers among Jordanian patients with genetic diseases and supports the integration of PGx testing to optimize the use of drugs like antidepressants, clopidogrel, and warfarin.

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Data availability

Data are available with the corresponding author upon request. Conflicts of Interest: The authors declare no conflicts of interest.

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Acknowledgements

The authors would like to thank INNOVIA Biobank for supporting this research.

Funding

This research did not receive any funding.

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Authors and Affiliations

  1. Department of Basic Medical Sciences, Faculty of Medicine, Al-Balqa Applied University, Al-Salt, 19117, Jordan

    Yazun Jarrar

  2. School of Pharmacy, The University of Jordan, Amman, Jordan

    Nancy Hakooz

  3. INNOVIA Biobank- BioCell for Labs and Medical Research, Amman, 11192, Jordan

    Dina Abu Hashem, Mariam Homsi, Sufyan Ali Ajeen, Maher Al Ghedan, Rania Almasri, Amnah Bdier & Mohammed Alraqad

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Contributions

Conceptualization, YJ, NH, AB, and MA; methodology, DA, MH, SAA, MAG, and RA; formal analysis, YJ, DA, MH, and SAA; writing—original draft preparation, YJ DA; writing—review and editing, NH, AB, and MA. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Yazun Jarrar or Nancy Hakooz.

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Jarrar, Y., Hakooz, N., Hashem, D.A. et al. Genome-wide screening of pharmacogenomic biomarkers in jordanian patients with genetic disorders. Pharmacogenomics J 25, 28 (2025). https://doi.org/10.1038/s41397-025-00387-w

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