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Pulmonary fibrosis in relation to genetic loci in an inception cohort of patients with early rheumatoid arthritis from northern Sweden
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.ORCID iD: 0000-0001-8999-0925
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
Department of Medical Sciences, National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Sweden.
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2022 (English)In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 61, no 3, p. 943-952Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: Pulmonary manifestations in RA are common comorbidities. Interstitial lung disease (ILD), both idiopathic and in RA, has been associated with several genetic variants. We assessed pulmonary fibrosis (PF) in an inception cohort of RA patients in relation to genetic variants and disease-related factors.

METHODS: A total of 1466 early RA patients were consecutively included and followed prospectively from the index date until death or 31 December 2016. Clinical and laboratory data and treatment were continuously registered according to the Swedish Rheumatology Quality Register. DNA was available from 1184 patients and 571 151 genome-wide single-nucleotide polymorphisms (SNPs) were analysed. Thirteen identified genetic variants were extracted. At follow-up, the patients answered a questionnaire regarding disease progression and lung involvement that was validated by reviewing medical records and analysing radiological examinations.

RESULTS: The prevalence of PF was 5.6% and the annualized incidence rate was 5.0/1000 (95% CI 3.80, 6.54). Four SNPs were associated with PF in RA: rs35705950 [MUC5B; OR 2.5 (95% CI 1.5, 4.0), adjusted P-value = 0.00016, q-value = 0.0021]; rs111521887 [TOLLIP; OR 1.9 (95% CI 1.3, 2.8), adjusted P-value = 0.0014, q-value = 0.0092]; rs2609255 [FAM13A; OR 1.7 (95% CI 1.1, 2.5), adjusted P-value = 0.013, q-value = 0.055] and rs2736100 [TERT; OR 1.5 (95% CI 1.0, 2.2), adjusted P-value = 0.046, q-value = 0.15]. Older age and RF positivity were associated with increased risk, while MTX treatment was associated with a lower risk of PF.

CONCLUSIONS: Development of PF in an inception cohort of RA patients was associated with 4 of 12 ILD risk genes. RA-related factors except for age at diagnosis and RF positivity were of limited importance in PF development.

Place, publisher, year, edition, pages
British Society for Rheumatology , 2022. Vol. 61, no 3, p. 943-952
Keywords [en]
pulmonary fibrosis, rheumatoid arthritis, rs111521887 (TOLLIP), rs2609255 (FAM13A), rs2736100 (TERT), rs35705950 (MUC5B)
National Category
Rheumatology and Autoimmunity
Identifiers
URN: urn:nbn:se:umu:diva-193000DOI: 10.1093/rheumatology/keab441ISI: 000755870900001PubMedID: 33993221Scopus ID: 2-s2.0-85125552923OAI: oai:DiVA.org:umu-193000DiVA, id: diva2:1644408
Available from: 2022-03-14 Created: 2022-03-14 Last updated: 2023-09-05Bibliographically approved

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Jönsson, EliasLjung, LottaNorrman, EvaÄrlestig, LisbethRantapää-Dahlqvist, Solbritt

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