GENETIC POLYMORPHISM OF THERMOSENSITIVE CATION CHANNELS TRPM8 AS A FACTOR PREDISPOSING TO COLD AIRWAY HYPERRESPONSIVENESS IN PATIENTS WITH CHRONIC OBSTRUCTIVE LUNG DISEASES

The aim of the present study was to investigate the influence of TRPM8 single-nucleotide polymorphisms (SNP) on cold airway hyperresponsiveness in patients with chronic obstructive lung diseases. 140 patients with persistent bronchial asthma and chronic obstructive pulmonary disease were examined. All of them were genotyped for c.750G>C, c.1256G>A, c.3048C>T, c.3174C>G SNPs and underwent spirometry testing before and after 3-minute isocapnic cold air hyperventilation. We found that GC genotype and C allele carriers for SNP c.750G>C prevailed among subjects who reacted positively on the cold air bronchoprovocation. Affected heterozygotes had substantial fall of FEV₁ after the cold challenge while response in GG homozygotes was less prominent. There were no statistically significant associations with cold hyperresponsiveness status for the rest of studied SNPs. However, CC homozygotes for SNPs c.3048C>T and c.3174C>G appeared also to be predisposed to bronchoconstriction in response to cold air hyperventilation. Thus, the discovered associations prove the contribution of TRPM8 thermoreceptors into the development of airway response to low temperatures.

polymorphism, thermoreception, cold, TRPM8, airway hyperresponsiveness, bronchial asthma, chronic obstructive pulmonary disease

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