Protein Called TAS2R38 Linked to Respiratory Tract Complications in CF

Protein Called TAS2R38 Linked to Respiratory Tract Complications in CF
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Problems with a protein called TAS2R38 are linked to a greater risk of severe sinonasal disease and Pseudomonas aeruginosa lung infections early in life in people with cystic fibrosis (CF), a study reported.

These findings may help to identify high-risk patients, those with a dysfunctional form of TAS2R38, and improve approaches taken to prevent these respiratory tract complications.

The study, “TAS2R38 is a novel modifier gene in patients with cystic fibrosis,” was published in the journal Nature Scientific Reports.

CF is caused by mutations in the CFTR gene, which result in low to no production of CFTR, a protein that controls secretion of body fluids such as mucus. The deficiency leads to the buildup of a thick and sticky mucus that is poorly removed from the airways.

This environment is favorable to the growth of inhaled disease-causing microbes — particularly Pseudomonas aeruginosa, a highly antibiotic-resistant bacteria. The resulting chronic inflammation and infection cause progressive lung damage.

Sinonasal disease (affecting the nasal passage and paranasal sinuses), particularly chronic sinusitis, is also common in people with CF. Some patients develop other airflow-obstructing sinonasal complications, such as turbinate hypertrophy and nasal polyps, which can require surgery — the final, most advanced step of sinonasal disease.

Increasing evidence suggests that CFTR mutations are not the only contributor to CF disease course. Other genes, inherited independently of CFTR, may “modulate the clinical manifestation and complications of patients with CF,” the researchers wrote.

Notably, previous studies suggest that additional contributors must exist for CF patients to develop nasal polyps requiring surgery and chronic P. aeruginosa lung infections.

A team of researchers at University of Naples Federico II, in Italy, identified a gene, called TAS2R38, that contributes to the risk of developing such complications in CF patients.

The TAS2R38 gene contains the instructions to produce TAS2R38, a protein receptor located on the surface of specific cells in the tongue, nose, and upper respiratory tract.

While it works as a bitter taste receptor in the tongue to protect against ingesting toxic substances — namely products of bacteria such as P. aeruginosa — in spoiled foods, it promotes immune responses against these bacterial products in the upper respiratory tract.

Previous studies have shown that these immune responses are strongly reduced in people carrying a “nonfunctional” copy of the TAS2R38 gene — which results in a deficient TAS2R38 receptor — compared with those carrying a “functional” copy. [Of note, all individuals inherit two copies of a gene, one from the mother and one from the father.]

For this reason, researchers analyzed the presence of the functional TAS2R38 copy in 210 CF patients (105 males and 105 females) and 95 healthy individuals (38 males and 57 females), and for its potential association with the severity of sinonasal disease and the occurrence of P. aeruginosa lung infections.

The median age of CF patients was 20 (range 5–65), and that of healthy volunteers was 18 (range 7–66). Two sinonasal conditions were assessed: turbinate hypertrophy, and nasal polyps requiring surgery (a more severe condition).

Results showed that the frequency of the functional TAS2R38 gene copy was significantly lower in CF patients with nasal polyps requiring surgery (33.7%), and in those with P. aeruginosa lung infections (38.4%), compared with its frequency in healthy people (54.2%).

These differences were even more pronounced in patients developing either complication before the age of 14 — 26.4% for surgery-requiring nasal polyps, and 31.1% for P. aeruginosa infections.

No significant differences in frequency were found between healthy individuals and CF patients without sinonasal conditions or P. aeruginosa infections, and those with turbinate hypertrophy.

Similar results were also evident when comparing the proportion of CF patients carrying both TAS2R38 functional copies to that of healthy individuals.

An analysis of 34 siblings of CF patients suggested that the presence of the functional TAS2R38 gene copy was protective against these complications.

Based on the findings, the team concluded that TAS2R38 may be considered “a novel modifier gene of sinonasal disease severity and of pulmonary P. aeruginosa colonization in patients with CF,” they wrote.

Importantly, CF patients carrying nonfunctional TAS2R38 copies may be at greater risk of severe respiratory tract complications, especially at young ages. Awareness of this possibility may help in finding better ways of preventing such complications, particularly life-threatening P. aeruginosa infections, in high-risk patients.

Marta Figueiredo holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from the University of Lisbon, Portugal. She is currently finishing her PhD in Biomedical Sciences at the University of Lisbon, where she focused her research on the role of several signalling pathways in thymus and parathyroid glands embryonic development.
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Patrícia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.

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Marta Figueiredo holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from the University of Lisbon, Portugal. She is currently finishing her PhD in Biomedical Sciences at the University of Lisbon, where she focused her research on the role of several signalling pathways in thymus and parathyroid glands embryonic development.
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