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Introduction <p>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.</p> Aim <p>This study aimed to screen the frequency of clinically relevant PGx biomarkers among a sample of Jordanian patients with genetic disorders.</p> Methods <p>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.</p> Result <p>In Phase I enzymes, <i>CYP2D6*10 (13.2%) and CYP2C19*</i>1/*<i>17 (18.4%)</i> were most common, while <i>CYP2C9</i> and <i>CYP3A4</i> variants were less frequent. In Phase II enzymes, <i>UGT1A1</i>80 + 2B appeared in 7.9% and multiple <i>DPYD</i> variants found in heterozygous forms 925%). Among toxicity-related markers, <i>G6PD</i> and <i>HLA-B*57:01</i> were detected in 3.9 and 2.6%, respectively. Transporter gene variants in <i>SLCO1B1</i> (15%) and <i>ABCB1</i> (21.1%) were relatively frequent. For pharmacodynamic genes, <i>VKORC1 −1639G</i> &gt; <i>A</i> (52.6%) and <i>CYP4F2 V433M</i> (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.</p>

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

  • 期刊论文

  • 发表日期：

    2025年10月18日

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  • Yazun Jarrar,
  • Nancy Hakooz,
  • Dina Abu Hashem,
  • Mariam Homsi,
  • Sufyan Ali Ajeen,
  • Maher Al Ghedan,
  • Rania Almasri,
  • Amnah Bdier,
  • Mohammed Alraqad

摘要

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.