التفاصيل البيبلوغرافية
| العنوان: |
Genome-wide investigation of persistence with methotrexate treatment in early rheumatoid arthritis. |
| المؤلفون: |
Sysojev, Anton Öberg, Saevarsdottir, Saedis, Diaz-Gallo, Lina-Marcela, Silberberg, Gilad N, Alfredsson, Lars, Klareskog, Lars, Baecklund, Eva, Björkman, Lena, Kastbom, Alf, Rantapää-Dahlqvist, Solbritt, Turesson, Carl, Jonsdottir, Ingileif, Stefansson, Kari, Frisell, Thomas, Padyukov, Leonid, Askling, Johan, Westerlind, Helga |
| المصدر: |
Rheumatology; May2024, Vol. 63 Issue 5, p1221-1229, 9p |
| مصطلحات موضوعية: |
CHRONIC disease risk factors, RHEUMATOID arthritis risk factors, GENETICS of rheumatoid arthritis, INFECTION risk factors, RISK assessment, GENOME-wide association studies, EARLY medical intervention, RESEARCH funding, RHEUMATOID arthritis, METHOTREXATE, TREATMENT effectiveness, ANTIRHEUMATIC agents, DESCRIPTIVE statistics, RELATIVE medical risk, SINGLE nucleotide polymorphisms |
| مصطلحات جغرافية: |
SWEDEN |
| مستخلص: |
Objectives To investigate the influence of genetic factors on persistence with treatment of early RA with MTX monotherapy. Methods We conducted a genome-wide association study (GWAS) in a sample of 3902 Swedish early-RA patients initiating MTX in DMARD monotherapy as their first-ever DMARD. The outcome, short- and long-term MTX treatment persistence, was defined as remaining on MTX at 1 and at 3 years, respectively, with no additional DMARDs added. As genetic predictors, we investigated individual SNPs, and then calculated a polygenic risk score (PRS) based on SNPs associated with RA risk. The SNP-based heritability of persistence was estimated overall and by RA serostatus. Results No individual SNP reached genome-wide significance (P < 5 × 10−8), either for persistence at 1 year or at 3 years. The RA PRS was not significantly associated with MTX treatment persistence at 1 year [relative risk (RR) = 0.98 (0.96–1.01)] or at 3 years [RR = 0.96 (0.93–1.00)]. The heritability of MTX treatment persistence was estimated to be 0.45 (0.15–0.75) at 1 year and 0.14 (0–0.40) at 3 years. The results in seropositive RA were comparable with those in the analysis of RA overall, while heritability estimates and PRS RRs were attenuated towards the null in seronegative RA. Conclusion Despite being the largest GWAS on an MTX treatment outcome to date, no genome-wide significant associations were detected. The modest heritability observed, coupled with the broad spread of suggestively associated loci, indicate that genetic influence is of polygenic nature. Nevertheless, MTX monotherapy persistence was lower in patients with a greater genetic disposition, per the PRS, towards RA. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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