Portal de investigação
Polymorphisms and haplotypes of TOLLIP and MUC5B are associated with susceptibility and survival in patients with fibrotic hypersensitivity pneumonitis
Data de publicação:
Autores da FMUP
Participantes de fora da FMUP
- Mota P.C.
- Soares M.L.
- Ferreira A.C.
- Santos R.F.
- Rufo J.C.
- Vasconcelos D.
- Carvalho A.
- Guimarães S.
- Vasques-Nóvoa F.
- Cardoso C.
- Melo N.
- Alexandre A.T.
- Coelho D.
- Morais A.
Unidades de investigação
Abstract
Introduction and Objectives: Hypersensitivity pneumonitis (HP) is an interstitial lung disease with diverse clinical features that can present a fibrotic phenotype similar to idiopathic pulmonary fibrosis (IPF) in genetically predisposed individuals. While several single nucleotide polymorphisms (SNPs) have been associated with IPF, the genetic factors contributing to fibrotic HP (fHP) remain poorly understood. This study investigated the association of MUC5B and TOLLIP variants with susceptibility, clinical presentation and survival in Portuguese patients with fHP. Material and Methods: A case-control study was undertaken with 97 fHP patients and 112 controls. Six SNPs residing in the MUC5B and TOLLIP genes and their haplotypes were analyzed. Associations with risk, survival, and clinical, radiographic, and pathological features of fHP were probed through comparisons among patients and controls. Results: MUC5B rs35705950 and three neighboring TOLLIP variants (rs3750920, rs111521887, and rs5743894) were associated with increased susceptibility to fHP. Minor allele frequencies were greater among fHP patients than in controls (40.7% vs 12.1%, P<0.0001; 52.6% vs 40.2%, P = 0.011; 22.7% vs 13.4%, P = 0.013; and 23.2% vs 12.9%, P = 0.006, respectively). Haplotypes formed by these variants were also linked to fHP susceptibility. Moreover, carriers of a specific haplotype (G-T-G-C) had a significant decrease in survival (adjusted hazard ratio 6.92, 95% CI 1.73–27.64, P = 0.006). Additional associations were found between TOLLIP rs111521887 and rs5743894 variants and decreased lung function at baseline, and the MUC5B SNP and radiographic features, further highlighting the influence of genetic factors in fHP. Conclusion: These findings suggest that TOLLIP and MUC5B variants and haplotypes may serve as valuable tools for risk assessment and prognosis in fibrotic hypersensitivity pneumonitis, potentially contributing to its patient stratification, and offer insights into the genetic factors influencing the clinical course of the condition. © 2024 Sociedade Portuguesa de Pneumologia
Dados da publicação
- ISSN/ISSNe:
- 2531-0429, 2531-0437
- Tipo:
- Article
- Páginas:
- -
- Link para outro recurso:
- www.scopus.com
Pulmonology Elsevier Espana
Citações Recebidas na Web of Science: 1
Citações Recebidas na Scopus: 2
Documentos
- Não há documentos
Filiações
Keywords
- Aged; Alveolitis, Extrinsic Allergic; Case-Control Studies; Female; Gene Frequency; Genetic Predisposition to Disease; Haplotypes; Humans; Idiopathic Pulmonary Fibrosis; Intracellular Signaling Peptides and Proteins; Male; Middle Aged; Mucin-5B; Polymorphism, Single Nucleotide; Portugal; MUC5B protein, human; mucin 5B; signal peptide; TOLLIP protein, human; aged; allergic pneumonitis; case control study; diagnosis; epidemiology; female; fibrosing alveolitis; gene frequency; genetic predisposition; genetics; haplotype; human; male; middle aged; mortality; Portugal; single nucleotide polymorphism
Financiamento
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Citar a publicação
Mota PC,Soares ML,Ferreira AC,Santos RF,Rufo JC,Vasconcelos D,Carvalho A,Guimarães S,Vasques F,Cardoso C,Melo N,Alexandre AT,Coelho D,Novais H,Morais A. Polymorphisms and haplotypes of TOLLIP and MUC5B are associated with susceptibility and survival in patients with fibrotic hypersensitivity pneumonitis. Pulmonology. 2024. 31. (1):2416788. IF:11,700. (1).
