Universität zu Köln

Trojan, T., Alcazar, Miguel A. Alejandre, Fink, G., Thomassen, J. C., Maessenhausen, M., V, Rietschel, E., Schneider, P. M. and Van Koningsbruggen-Rietschel, S. (2022). The effect of TGF-beta(1) polymorphisms on pulmonary disease progression in patients with cystic fibrosis. BMC Pulm. Med., 22 (1). LONDON: BMC. ISSN 1471-2466

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Abstract

Background: Transforming Growth Factor-beta(1) (TGF-beta(1)) is a genetic modifier in patients with cystic fibrosis (CF). Several single nucleotide polymorphisms (SNPs) of TGF-beta(1) 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-beta(1) polymorphisms and pulmonary disease progression in CF patients. Furthermore, the effect of TGF-beta(1) polymorphisms on inflammatory cytokines in sputum was investigated. Methods: 56 CF-patients and 62 controls were genotyped for three relevant SNPs in their TGF-beta(1) sequence using the SNaPshot (R) 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-1 beta, IL-8, IL-6,TNF-alpha 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 ofTNF-alpha (p < 0,05). Higher levels of TGF-beta(1) 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-beta(1) 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-beta(1) inhibition could potentially be developed as a new therapeutic option to modulate CF lung disease.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Trojan, T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Alcazar, Miguel A. Alejandre UNSPECIFIED UNSPECIFIED UNSPECIFIED Fink, G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Thomassen, J. C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Maessenhausen, M., V UNSPECIFIED UNSPECIFIED UNSPECIFIED Rietschel, E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schneider, P. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Van Koningsbruggen-Rietschel, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-669351
DOI:	10.1186/s12890-022-01977-1
Journal or Publication Title:	BMC Pulm. Med.
Volume:	22
Number:	1
Date:	2022
Publisher:	BMC
Place of Publication:	LONDON
ISSN:	1471-2466
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TRANSFORMING GROWTH-FACTOR-BETA-1; ASSOCIATION; CHILDREN; DECLINE Multiple languages Respiratory System Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/66935