Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 May 7;22(1):183.
doi: 10.1186/s12890-022-01977-1.

The effect of TGF-β1 polymorphisms on pulmonary disease progression in patients with cystic fibrosis

T Trojan  1 , Miguel A Alejandre Alcazar  2   3 , G Fink  2 , J C Thomassen  4 , M V Maessenhausen  4 , E Rietschel  4 , P M Schneider  5 , S van Koningsbruggen-Rietschel  4
Affiliations

The effect of TGF-β1 polymorphisms on pulmonary disease progression in patients with cystic fibrosis

T Trojan et al. BMC Pulm Med. .

Abstract

Background: Transforming Growth Factor-β1 (TGF-β1) is a genetic modifier in patients with cystic fibrosis (CF). Several single nucleotide polymorphisms (SNPs) of TGF-β1 are associated with neutrophilic inflammation, lung fibrosis and loss of pulmonary function.

Aim: The aim of this study was to assess the relationship between genetic TGF-β1 polymorphisms and pulmonary disease progression in CF patients. Furthermore, the effect of TGF-β1 polymorphisms on inflammatory cytokines in sputum was investigated.

Methods: 56 CF-patients and 62 controls were genotyped for three relevant SNPs in their TGF-β1 sequence using the SNaPshot® technique. Individual "slopes" in forced expiratory volume in 1 s (FEV1) for all patients were calculated by using documented lung function values of the previous five years. The status of Pseudomonas aeruginosa (Pa) infection was determined. Sputum concentrations of the protease elastase, the serine protease inhibitor elafin and the cytokines IL-1β, IL-8, IL-6, TNF-α were measured after a standardized sputum induction and processing.

Results: The homozygous TT genotype at codon 10 was associated with a lower rate of chronic Pa infection (p < 0.05). The heterozygous GC genotype at codon 25 was associated with lower lung function decline (p < 0.05). Patients with homozygous TT genotype at the promotor SNP showed higher levels of TNF-α (p < 0,05). Higher levels of TGF-β1 in plasma were associated with a more rapid FEV1 decline over five years (p < 0.05).

Conclusions: Our results suggest that polymorphisms in the TGF-β1 gene have an effect on lung function decline, Pa infection as well as levels of inflammatory cytokines. Genotyping these polymorphisms could potentially be used to identify CF patients with higher risk of disease progression. TGF-β1 inhibition could potentially be developed as a new therapeutic option to modulate CF lung disease.

Keywords: Cystic fibrosis; Forced expiratory volume in one second (FEV1); Inflammation; Polymorphisms; Pseudomonas aeruginosa; Transforming-growth-factor Beta 1 (TGF-β1).

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
TGF- β1 codon 10 SNP genotypes and prevalence of Pa infection status within the genotype group
Fig. 2
Fig. 2
TGF- β1 plasma concentration and FEV1 slope of CF patients
Fig. 3
Fig. 3
a TGF- β1 sputum concentration and FEV1 slope group, b TGF- β1 sputum concentration and FEV1 group over five years
Fig. 4
Fig. 4
TGF-β1 Promotor SNP genotype group and TNF-α concentration in sputum
See this image and copyright information in PMC

References

    1. De Boeck K. Progress in therapies for cystic fibrosis. Lancet Respir Med. 2016;2016(4):662–674. doi: 10.1016/S2213-2600(16)00023-0. - DOI - PubMed
    1. Rafeeq MM. Cystic fibrosis: current therapeutic targets and future approaches. J Transl Med. 2017;15(1):84. doi: 10.1186/s12967-017-1193-9. - DOI - PMC - PubMed
    1. Eickmeier O (2013) Transforming growth factor b1 genotypes in relation to tgfb1, IL-8, TNF-alpha in induced sputum and blood in cystic fibrosis. Mediators Inflamm. 10.1155/2013/913135. - PMC - PubMed
    1. Nichols D. Inflammation and its genesis in cystic fibrosis. Pediatr Pulmonol. 2015;50:39–56. doi: 10.1002/ppul.23242. - DOI - PubMed
    1. Jaurent GJ. Encyclopedia of respiratory medicine. Academic Press; 2006.