ORIGINAL RESEARCH article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
This article is part of the Research TopicBiologics and Targeted Therapies for Autoimmune and Auto-inflammatory Dermatoses: Balancing Efficacy with Safety and ToxicityView all 5 articles
Pharmacogenomic landscape of TNF inhibitors in the Middle Eastern Qatari population
Provisionally accepted
- 1Hamad bin Khalifa University, Doha, Qatar
- 2Queen Mary University of London, London, United Kingdom
- 3University of Liverpool, Liverpool, United Kingdom
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Tumor necrosis factor alpha (TNF-α) is an important cytokine that frequently contributes to the pathogenicity of autoimmune diseases. Therefore, TNF inhibitors (TNFi) are used to treat autoimmune diseases. However, around 40% of the patients do not respond to TNFi, with genetic variants being a contributor to this variance. The prevalence of genetic variants affecting TNFi response in Middle Eastern populations is still not understood. We assess the distribution of variants in 111 genes associated with TNFi in 14,387 Qatari individuals using whole genome sequencing data. Of the 151 known pharmacogenomic variants associated with response to TNFi, approximately half have significantly different allele frequency distribution in the Qatari population compared to other world populations from the gnomAD dataset. High frequency of rs1800629 (TNF), rs1800896 (IL10), and rs1143634 (IL1B) variants are observed, which are known to be associated with responses to Etanercept and Infliximab. Moreover, we identified that PSORS1C1 has the highest CAPLoF (cumulative allele probability) scores for loss-of-function variants, which is associated with response to Etanercept and Adalimumab. The findings of this study will enhance our understanding of the pharmacogenomics of TNF inhibitors in Qatar and beyond, while also supporting the study of genetics in underrepresented populations.
Keywords: TNF inhibitors, whole genome sequencing, precision medicine, pharmacogenomics, Qatar, Autoimmune Diseases, drug response
Received: 28 Jul 2025; Accepted: 30 Oct 2025.
Copyright: © 2025 Jan, Velayutham, Mifsud and Jithesh. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Puthen Veettil Jithesh, jveettil@hbku.edu.qa
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