TGF-beta1 Genetic Variations Linked to Lung Health, Pseudomonas Risk

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Certain variations in the gene that codes for the inflammatory signaling molecule TGF-beta1 are associated with faster lung function decline and a higher risk of Pseudomonas infections for people with cystic fibrosis (CF), a new study indicates.

“Our results demonstrate the relevance of the multifunctional cytokine [signaling molecule] TGF-[beta]1 as a genetic modifier in patients with CF,” its researchers wrote, noting that these genetic variations may be useful for predicting a person’s risk of disease progression.

The study, “The effect of TGF-β1 polymorphisms on pulmonary disease progression in patients with cystic fibrosis,” was published in BMC Pulmonary Medicine.

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TGF-beta1 is a signaling protein that plays central roles in coordinating a number of processes related to inflammation and wound healing. Certain variations in the code of the gene that provides instructions for making this protein may alter its levels and/or activity, which could have ramifications in CF.

Scientists in Germany conducted an analysis aiming to identify how variations in the TGF-beta1 gene might impact CF progression. Lung function was assessed by measuring forced expiratory volume in one second (FEV1), which tests how much air a person can quickly and forcefully exhale.

The analysis included data for 56 CF patients, as well as 62 healthy individuals as controls. Among the CF patients, the mean age was 21, and about 1 in 3 were chronically infected with Pseudomonas aeruginosa, the main bacterial agent in CF lung infections.

Researchers assessed the impacts of three single nucleotide polymorphisms, or SNPs, in the gene coding TGF-beta1. A SNP is a change in one nucleotide, or “letter” of the genetic code. Since everyone has two copies of the gene, one inherited from each biological parent, an individual’s genotype for any given SNP can be represented by two letters, representing the two nucleotides at that location in each gene copy.

Results showed that patients with a GC genotype at codon 25 (a particular spot in the gene) were more likely to have FEV1 scores that increased over time, suggesting improving lung function. Among CF patients with this genotype, 66.7% had FEV1 scores rising at a rate greater than 1% per year. Such an increase was seen in only 10.2% of those with a GG genotype at the same location.

Variations in another part of the gene, codon 10, were associated with Pseudomonas infection risk. Specifically, individuals with a TT genotype were less likely to be infected than those with CC or CT genotypes — 16.7% of patients with the TT genotype were infected with Pseudomonas, compared with 42.1% of those with CC or CT genotypes.

A third TGF-beta1 SNP in the analysis was not associated with lung function or infection risk. However, researchers noted that those with a TT genotype in this region, located in the gene’s promoter, had markedly higher sputum levels of another pro-inflammatory signaling molecule called TNF-alpha.

“We showed that genetic polymorphisms [variations] in the TGF-[beta]1 sequence have an impact on pulmonary function, rates of chronic [Pseudomonas] infection as well as the concentration of inflammatory cytokines, such as TNF-[alpha],” the researchers concluded.

“TGF-[beta]1 polymorphisms might therefore be used to identify patients with a high risk for disease progression,” they added.