Association of bitter taste receptor TAS2R38 polymorphisms with smoking, asthma, functional and immunological abnormalities: a case–control study

Bitter taste receptors (TAS2R) are expressed not only in the oral cavity, but also in many tissues of the body, including various cells of the respiratory tract. Activation of TAS2R is accompanied by inhibition of the inflammatory process, improvement of mucociliary clearance and relaxation of bronchial smooth muscles – effects that are potentially beneficial for the treatment of asthma. Despite this, studies of the role of TAS2R gene polymorphisms in the pathogenesis of asthma remain scarce. The aim was to study the association of single nucleotide polymorphisms (SNPs) rs713598, rs1726866 and rs10246939 of the TAS2R38 gene with asthma, lung function and immunological markers in relation to the smoking status of the subjects. Methods. The case–control study enrolled 420 subjects, including 225 patients with asthma and 195 healthy individuals (control group). Lung function parameters were determined using spirometry. SNPs were genotyped using asymmetric PCR with oligonucleotide probe melting analysis or PCR with high-resolution melting analysis of amplification products. Cytokine concentrations were measured in serum using immunofluorescence assay on microbeads. Total IgE levels were assayed using enzyme immunoassay. Results. We found that the AVI/AVI diplotype was more common in asthma patients who smoked compared to non-smokers after adjustment for gender and age (OR 2.0 95% CI (1.06 – 3.63); p = 0.03), but it was not associated with smoking in the control group. In smokers, this diplotype contributed to the development of asthma regardless of gender, age, and pack-year index (OR 2.1 95% CI (1.07 – 4.22); p = 0.03). In addition, the AVI/AVI diplotype was associated with severe bronchial obstruction (FEV1 < 60 %) in patients with asthma after adjustment for gender, age, and pack-year index (OR 2.3 95 % CI (1.14 – 4.78); p = 0.02). Finally, carriers of the AVI/AVI diplotype were characterized by higher serum IL-6 levels (10.5 (6.2 – 20.2) pg/ml) compared to AVI/ PAV heterozygotes (6.7 (2.5 – 11.4) pg/ml; p = 0.005) and PAV/PAV homozygotes (6.4 (4.3 – 9.4) pg/ml; p = 0.01). Conclusion. The AVI/AVI diplotype encoding a nonfunctional variant of TAS2R38 receptor is associated with a predisposition to smoking in patients with asthma, a predisposition to the development of asthma in smokers, as well as with severe bronchial obstruction and increased IL-6 production in the studied patients.