Background Pseudomonas aeruginosa (Pa) mediates several virulence factors through quorum sensing (QS). Intriguing in vitro data suggests Pa QS molecules are ‘sensed’ by the T2R38 receptor on airway cilia (J Clin Invest, 2012;122:4145–59), leading to changes in ciliary beat frequency and nitric oxide production, possibly enhancing bacterial clearance. Three polymorphisms occur in the gene coding this receptor, altering the amino acid sequence and receptor function; the functional allele has proline-alanine-valine (PAV); the non-functional allele has alanine-valine-isoleucine (AVI). We hypothesised that the T2R38 receptor may be important in Pa host defence in people with cystic fibrosis (CF) and that T2R38 genotype may modify infection status and clinical outcomes.
Methods Patients over 6 years with CF were genotyped for polymorphisms in the TAS2R38 gene. Pa infection status was determined by review of all respiratory cultures during 2014 and assigned according to Leeds criteria as chronic, intermittent, Pa free or never. Only patients with ≥3 cultures/year were included in analysis. Lung function data was obtained from CF annual reviews during 2014.
Results T2R38 receptor genotypes were obtained for 271 patients: 83 (30.6%) AVI/AVI, 44 (16.2%) PAV/PAV, 116 (42.8%) AVI/PAV and 28 (10.3%) AVI/other or PAV/other. Between AVI/AVI, PAV/PAV and AVI/PAV groups there was no significant difference in median age, gender or p.Phe508del CFTR mutation frequency. By T2R38 genotype, there was no significant difference in the proportion of patients in each Pa infection category. In patients with intermittent or chronic Pa there was no significant difference by T2R38 genotype in mean percent predicted FEV1 or FVC.
Conclusion T2R38 genotype does not appear to modify Pa infection in people with CF, or to modify lung disease severity in people with CF and intermittent or chronic Pa infection. Further work is underway to investigate T2R38-dependant responses to Pa in vitro.