The pulmonary fibrosis-associated MUC5B promoter polymorphism does not influence the development of interstitial pneumonia in systemic sclerosis
- PMID: 22576636
- PMCID: PMC3515031
- DOI: 10.1378/chest.12-0110
The pulmonary fibrosis-associated MUC5B promoter polymorphism does not influence the development of interstitial pneumonia in systemic sclerosis
Abstract
Background: More than 80% of patients with systemic sclerosis (SSc) develop lung involvement, most commonly interstitial pneumonia (IP). We recently identified a common variant in the promoter region of MUC5B (rs35705950) that has a significant effect on the risk of developing both familial and sporadic forms of IP. We hypothesized that this MUC5B promoter polymorphism is also associated with IP in subjects with SSc.
Methods: We examined the minor allele frequency of the MUC5B polymorphism among 231 subjects with SSc, 109 with IP, and 122 without IP. IP diagnosis was confirmed by HRCT imaging and defined as the presence of reticular infiltrates and/or honeycomb cysts. FVC and diffusing capacity of the lung for carbon monoxide (Dlco) were also assessed.
Results: We found no association between IP and the MUC5B polymorphism among subjects with SSc (OR = 1.1, P = .80). The frequencies of the MUC5B polymorphism among subjects with SSc with IP (10.6%) and without IP (9.4%) were similar to the frequency observed in a population of unaffected control subjects (9.0%). In secondary analyses, we found the MUC5B polymorphism was not significantly associated with either FVC (P = .42) or Dlco (P = .06). No association with SSc-associated IP was found even when we used a more conservative definition of IP (FVC ≤ 70% and evidence of reticulations or honeycombing vs SSc FVC > 70% and no evidence of reticulation or honeycombing).
Conclusions: Although SSc-associated IP is clinically, radiologically, and histologically similar to other forms of IP, it appears to have distinct genetic risk factors. This study highlights the genetic and phenotypic heterogeneity of IP in general.
Figures
Similar articles
-
Mucin 5B promoter polymorphism is associated with idiopathic pulmonary fibrosis but not with development of lung fibrosis in systemic sclerosis or sarcoidosis.Thorax. 2013 May;68(5):436-41. doi: 10.1136/thoraxjnl-2012-201786. Epub 2013 Jan 15. Thorax. 2013. PMID: 23321605
-
A common MUC5B promoter polymorphism and pulmonary fibrosis.N Engl J Med. 2011 Apr 21;364(16):1503-12. doi: 10.1056/NEJMoa1013660. N Engl J Med. 2011. PMID: 21506741 Free PMC article.
-
The MUC5B promoter variant does not predict progression of interstitial lung disease in systemic sclerosis.Semin Arthritis Rheum. 2020 Oct;50(5):963-967. doi: 10.1016/j.semarthrit.2020.06.003. Epub 2020 Jun 16. Semin Arthritis Rheum. 2020. PMID: 32906032 Free PMC article. Clinical Trial.
-
Integrating Genomics Into Management of Fibrotic Interstitial Lung Disease.Chest. 2019 May;155(5):1026-1040. doi: 10.1016/j.chest.2018.12.011. Epub 2019 Jan 17. Chest. 2019. PMID: 30660786 Free PMC article. Review.
-
The MUC5B variant is associated with idiopathic pulmonary fibrosis but not with systemic sclerosis interstitial lung disease in the European Caucasian population.PLoS One. 2013 Aug 5;8(8):e70621. doi: 10.1371/journal.pone.0070621. Print 2013. PLoS One. 2013. PMID: 23940607 Free PMC article. Review.
Cited by
-
Genetics and Genomics of Pulmonary Fibrosis: Charting the Molecular Landscape and Shaping Precision Medicine.Am J Respir Crit Care Med. 2024 Aug 15;210(4):401-423. doi: 10.1164/rccm.202401-0238SO. Am J Respir Crit Care Med. 2024. PMID: 38573068 Review.
-
Clinical characteristics of patients with connective tissue disease-related interstitial lung disease: a retrospective analysis.Clin Rheumatol. 2024 May;43(5):1693-1701. doi: 10.1007/s10067-024-06926-3. Epub 2024 Mar 9. Clin Rheumatol. 2024. PMID: 38459356
-
Serum Oncomarkers in Patients with MPO-ANCA-Positive Vasculitis: Diagnostic and Prognostic Predictive Values for Interstitial Lung Disease.Lung. 2022 Jun;200(3):331-338. doi: 10.1007/s00408-022-00532-3. Epub 2022 Apr 15. Lung. 2022. PMID: 35426513
-
Biomarkers of connective tissue disease-associated interstitial lung disease in bronchoalveolar lavage fluid: A label-free mass spectrometry-based relative quantification study.J Clin Lab Anal. 2022 May;36(5):e24367. doi: 10.1002/jcla.24367. Epub 2022 Mar 25. J Clin Lab Anal. 2022. PMID: 35334492 Free PMC article.
-
Connective Tissue Growth Factor Single Nucleotide Polymorphisms in (Familial) Pulmonary Fibrosis and Connective Tissue Disease Associated Interstitial Lung Disease.Lung. 2021 Dec;199(6):659-666. doi: 10.1007/s00408-021-00494-y. Epub 2021 Nov 23. Lung. 2021. PMID: 34812907
References
-
- Ferri C, Valentini G, Cozzi F, et al. ; Systemic Sclerosis Study Group of the Italian Society of Rheumatology (SIR-GSSSc) Systemic sclerosis: demographic, clinical, and serologic features and survival in 1,012 Italian patients. Medicine (Baltimore). 2002;81(2):139-153 - PubMed
-
- Bouros D, Wells AU, Nicholson AG, et al. Histopathologic subsets of fibrosing alveolitis in patients with systemic sclerosis and their relationship to outcome. Am J Respir Crit Care Med. 2002;165(12):1581-1586 - PubMed
-
- Wells AU, Cullinan P, Hansell DM, et al. Fibrosing alveolitis associated with systemic sclerosis has a better prognosis than lone cryptogenic fibrosing alveolitis. Am J Respir Crit Care Med. 1994;149(6):1583-1590 - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Miscellaneous