Journal
RHEUMATOLOGY
Volume 61, Issue 3, Pages 943-952Publisher
OXFORD UNIV PRESS
DOI: 10.1093/rheumatology/keab441
Keywords
rheumatoid arthritis; pulmonary fibrosis; rs35705950 (MUC5B); rs111521887 (TOLLIP); rs2609255 (FAM13A); rs2736100 (TERT)
Categories
Funding
- Vasculitis Foundation USA
- Swedish Research Council [K2013-52X-20307-07-3, 2018-02551]
- King Gustaf V's 80-Year Fund
- Swedish Rheumatism Association
- Umea University
- Swedish Research Council [2018-02551] Funding Source: Swedish Research Council
- Vinnova [2018-02551] Funding Source: Vinnova
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This study assessed the association between pulmonary fibrosis (PF) and genetic variants and disease-related factors in rheumatoid arthritis (RA) patients. The results showed that PF in RA patients is associated with four genetic variants. Older age and RF positivity are associated with increased risk, while MTX treatment is associated with a lower risk of PF development.
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.
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