Velayutham Dinesh, Bastaki Kholoud, Irfan Areeba, Abuhaliqa Mohammed, AlMulla Aisha, Ghuloum Suhaila, Azeem Muhammad Waqar, Pirmohamed Munir, Jithesh Puthen Veettil
College of Health & Life Sciences, Hamad Bin Khalifa University, Doha, Qatar.
College of Pharmacy, QU Health, Qatar University, Doha, Qatar.
Camb Prism Precis Med. 2025 Apr 28;3:e4. doi: 10.1017/pcm.2025.2. eCollection 2025.
Consortia like the Clinical Pharmacogenetic Implementation Consortium (CPIC) and the Dutch Pharmacogenetic Working Group (DPWG) provide clinical guidelines but pharmacogenomics implementation depends on population prevalence of actionable genetic variants and response phenotypes. We analyzed the distribution of actionable genetic variants and clinical recommendations in 14,354 adult Qataris, focusing only genes with guidelines (, , and ). Haplotypes and diplotypes were generated from 490 alleles using whole genome data and metabolizer phenotypes were predicted based on current knowledge. Qatari population predicted to have actionable metabolizer phenotypes of CYP2C19, CYP2B6 and CYP2D6 impacting response to antidepressants were in the range of 1%-58% and for antipsychotics 0.1%-33% based on and Fine-grained analysis based on clinical guidelines also revealed that while the Qataris may need prescription of an alternate antidepressant not metabolized by CYP2C19, patients from other populations may just need altering the dosage of tricyclic antidepressants like amitriptyline. Further studies incorporating other factors such as diet, environment and cultural habits alongwith population-specific variants will help in the pharmacogenomics implementation in the Qatari population.
像临床药物基因组学实施联盟(CPIC)和荷兰药物基因组学工作组(DPWG)这样的联盟提供临床指南,但药物基因组学的实施取决于可操作基因变异和反应表型的人群患病率。我们分析了14354名成年卡塔尔人的可操作基因变异分布和临床建议,仅关注有指南的基因(、、和)。利用全基因组数据从490个等位基因中生成单倍型和双倍型,并根据现有知识预测代谢表型。根据和,预计卡塔尔人群中具有影响抗抑郁药反应的CYP2C19、CYP2B6和CYP2D6可操作代谢表型的比例在1%至58%之间,抗精神病药物的比例在0.1%至33%之间。基于临床指南的细粒度分析还显示,虽然卡塔尔人可能需要开具不由CYP2C19代谢的替代抗抑郁药,但其他人群的患者可能只需要改变三环类抗抑郁药(如阿米替林)的剂量。纳入饮食、环境和文化习惯等其他因素以及特定人群变异的进一步研究将有助于卡塔尔人群的药物基因组学实施。