Academic Journal
Expression quantitative trait loci analysis in rheumatoid arthritis identifies tissue specific variants associated with severity and outcome
| العنوان: | Expression quantitative trait loci analysis in rheumatoid arthritis identifies tissue specific variants associated with severity and outcome |
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| المؤلفون: | Goldmann, Katriona, Spiliopoulou, Athina, Iakovliev, Andrii, Plant, Darren, Nair, Nisha, Cubuk, Cankut, The MATURA Consortium, McKeigue, Paul, Barnes, Michael R, Barton, Anne, Pitzalis, Costantino, Lewis, Myles J |
| بيانات النشر: | BMJ Publishing Group Ltd |
| سنة النشر: | 2024 |
| المجموعة: | HighWire Press (Stanford University) |
| مصطلحات موضوعية: | Rheumatoid arthritis |
| الوصف: | Objective Genome-wide association studies have successfully identified more than 100 loci associated with susceptibility to rheumatoid arthritis (RA). However, our understanding of the functional effects of genetic variants in causing RA and their effects on disease severity and response to treatment remains limited. Methods In this study, we conducted expression quantitative trait locus (eQTL) analysis to dissect the link between genetic variants and gene expression comparing the disease tissue against blood using RNA-Sequencing of synovial biopsies (n=85) and blood samples (n=51) from treatment-nai&x0308;ve patients with RA from the Pathobiology of Early Arthritis Cohort. Results This identified 898 eQTL genes in synovium and genes loci in blood, with 232 genes in common to both synovium and blood, although notably many eQTL were tissue specific. Examining the HLA region, we uncovered a specific eQTL at HLA-DPB2 with the critical triad of single-nucleotide polymorphisms (SNPs) rs3128921 driving synovial HLA-DPB2 expression, and both rs3128921 and HLA-DPB2 gene expression correlating with clinical severity and increasing probability of the lympho-myeloid pathotype. Conclusions This analysis highlights the need to explore functional consequences of genetic associations in disease tissue. HLA-DPB2 SNP rs3128921 could potentially be used to stratify patients to more aggressive treatment immediately at diagnosis. |
| نوع الوثيقة: | text |
| وصف الملف: | text/html |
| اللغة: | English |
| Relation: | http://ard.bmj.com/cgi/content/short/83/3/288; http://dx.doi.org/10.1136/ard-2023-224540 |
| DOI: | 10.1136/ard-2023-224540 |
| الاتاحة: | http://ard.bmj.com/cgi/content/short/83/3/288 https://doi.org/10.1136/ard-2023-224540 |
| Rights: | Copyright (C) 2024, BMJ Publishing Group Ltd |
| رقم الانضمام: | edsbas.8CA6F8F6 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1136/ard-2023-224540 |
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