LAUSR

OBJECTIVES Pulmonary manifestations in rheumatoid arthritis (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 1466 early RA patients were consecutively included and followed prospectively from index date until death or December 31, 2016. Clinical, and laboratory data and treatment were continuously registered according to Swedish Rheumatology quality register. DNA was available from 1184 patients and 571 151 genome-wide-single-nucleotide polymorphism were analysed (GSA, Illumina, deCode, Island). Thirteen identified genetic variants were extracted. At follow-up the patients answered a questionnaire regarding disease progression and lung involvement, which 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 and q-value = 0.0021, rs111521887 (TOLLIP) OR = 1.9 (95%CI 1.3, 2.8), adjusted p-value = 0.0014 and q-value = 0.0092; rs2609255 (FAM13A) (OR = 1.7 (95%CI 1.1, 2.5), adjusted p-value = 0.013 and q-value = 0.055) and rs2736100 (TERT) OR = 1.5 (1.0, 2.2), adjusted p-value = 0.046, q-value was 0.15. Older age and rheumatoid factor-positivity were associated with increased risk, whilst methotrexate treatment was associated with a lower risk of PF. CONCLUSIONS Development of PF in an inception cohort of RA patients was associated with four of 12 ILD risk genes. RA-related factors except for age at diagnosis and RF-positivity were of limited importance in PF development.