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Pulmonary fibrosis in relation to genetic loci in an inception cohort of patients with early rheumatoid arthritis from northern Sweden

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-re...

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Autores principales: Jönsson, Elias, Ljung, Lotta, Norrman, Eva, Freyhult, Eva, Ärlestig, Lisbeth, Dahlqvist, Johanna, Rantapää-Dahlqvist, Solbritt
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8889303/
https://www.ncbi.nlm.nih.gov/pubmed/33993221
http://dx.doi.org/10.1093/rheumatology/keab441
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author Jönsson, Elias
Ljung, Lotta
Norrman, Eva
Freyhult, Eva
Ärlestig, Lisbeth
Dahlqvist, Johanna
Rantapää-Dahlqvist, Solbritt
author_facet Jönsson, Elias
Ljung, Lotta
Norrman, Eva
Freyhult, Eva
Ärlestig, Lisbeth
Dahlqvist, Johanna
Rantapää-Dahlqvist, Solbritt
author_sort Jönsson, Elias
collection PubMed
description 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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spelling pubmed-88893032022-03-02 Pulmonary fibrosis in relation to genetic loci in an inception cohort of patients with early rheumatoid arthritis from northern Sweden Jönsson, Elias Ljung, Lotta Norrman, Eva Freyhult, Eva Ärlestig, Lisbeth Dahlqvist, Johanna Rantapää-Dahlqvist, Solbritt Rheumatology (Oxford) Clinical Science 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. Oxford University Press 2021-05-16 /pmc/articles/PMC8889303/ /pubmed/33993221 http://dx.doi.org/10.1093/rheumatology/keab441 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Clinical Science
Jönsson, Elias
Ljung, Lotta
Norrman, Eva
Freyhult, Eva
Ärlestig, Lisbeth
Dahlqvist, Johanna
Rantapää-Dahlqvist, Solbritt
Pulmonary fibrosis in relation to genetic loci in an inception cohort of patients with early rheumatoid arthritis from northern Sweden
title Pulmonary fibrosis in relation to genetic loci in an inception cohort of patients with early rheumatoid arthritis from northern Sweden
title_full Pulmonary fibrosis in relation to genetic loci in an inception cohort of patients with early rheumatoid arthritis from northern Sweden
title_fullStr Pulmonary fibrosis in relation to genetic loci in an inception cohort of patients with early rheumatoid arthritis from northern Sweden
title_full_unstemmed Pulmonary fibrosis in relation to genetic loci in an inception cohort of patients with early rheumatoid arthritis from northern Sweden
title_short Pulmonary fibrosis in relation to genetic loci in an inception cohort of patients with early rheumatoid arthritis from northern Sweden
title_sort pulmonary fibrosis in relation to genetic loci in an inception cohort of patients with early rheumatoid arthritis from northern sweden
topic Clinical Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8889303/
https://www.ncbi.nlm.nih.gov/pubmed/33993221
http://dx.doi.org/10.1093/rheumatology/keab441
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