Association of <i>TAS2R3</i>, <i>TAS2R4</i> and <i>TAS2R5</i> gene polymorphism with predisposition to asthma

Abstract

Introduction. It is known that bitter taste receptors (TAS2R) are expressed on many cells of the respiratory system and their activation is accompanied by a wide range of potentially beneficial effects for the treatment of asthma.Aim. To evaluate the influence of TAS2R3, TAS2R4 and TAS2R5 polymorphisms on the development of asthma, parameters of lung function and control of the disease.Materials and methods. The study enrolled 240 patients with asthma of varying severity (mean age 43.9±1.03 years, 44.5% males) and 90 healthy volunteers (control group, mean age 38.0±1.09 years, 50% males). Lung function was assessed using standard spirometry, the disease control was determined by ACT questionnaire. Preliminary screening by minor allele frequency, prediction of functional significance and assessment of linkage disequilibrium allowed us to select TAS2R4 rs33920115 as a representative variant for the group of TAS2R3, TAS2R4 and TAS2R5 polymorphisms. Genotyping was performed by PCR with high-resolution melting analysis.Results. rs33920115 polymorphism was significantly associated with asthma in codominant (p=0.01), dominant (p=0.006), recessive (p=0.03), log-additive (p=0.003) and multiplicative (p=0.003) genetic models. Carriage of the AA genotype was more often observed among patients with asthma (29.2% vs. 17.8%) while the GG homozygotes were prevalent in the control group (33.3% vs. 19.2%). The effect remained significant after adjustment for sex and age (OR 1.8; 95%CI (1.26-2.61), p=0.001 for log-additive model). We found no effect of rs33920115 on lung function and asthma control.Conclusion. TAS2R4 rs33920115 polymorphism and associated variations in TAS2R3 and TAS2R5 genes may influence the predisposition to asthma development, probably due to changes in the expression of the corresponding receptors.