Year: 2025
Type: article
Study design: Observational Study
Abstract: Introduction 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. Methods We assessed the distribution of variants in 111 genes associated with TNFi in 14,387 Qatari individuals using whole genome sequencing data. Results 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 CAP LoF (cumulative allele probability) scores for loss-of-function variants, which is associated with response to Etanercept and Adalimumab. Discussion 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.
Source: Frontiers in Immunology
Authors: Zainab Jan, Dinesh Velayutham, Borbala Mifsud, Georges Nemer, Puthen Veettil Jithesh, Nady El Hajj, Ehsan Pourkarimi, Omar Albagha, Farah El Assadi, Zainab Jan, Dinesh Velayutham, Samar Al Emadi, Karima Becetti, Mohammed Hammoudeh, Hala Albakheet, Nour Hamad, Sanaa Sharari, Sharon Bout-Tabaku, Buthaina Al Adba, Mona El Chawli, Fathima Abubacker, Mamoun Elawad, Nazira Ibrahim, Borbala Mifsud, Puthen Veettil Jithesh
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W4416402955