TRPM8 gene polymorphisms and their relation to cold airway hyperresponsiveness in patients with bronchial asthma

Cold airway hyperresponsiveness (CAH) influences the clinical course of bronchial asthma (BA) leading to rapid deterioration of lung function in cold climate conditions. Transient receptor potential melastatin 8 (TRPM8) ion channels serve as a cold sensors and therefore may mediate airway constrictor responses to cold air. There are no data presented on the specific role of TRPM8 gene in CAH development. Objective: The main goal of our study was to investigate whether the variability in TRPM8 gene affects the state of CAH. Methods: 123 patients with BA were recruited. All of them underwent lung function testing before and after 3-minute isocapnic cold air hyperventilation challenge (ICAH). Four SNPs of TRPM8 gene were genotyped and tested for association with CAH: c.750G>C (rs11562975), c.1256G>A (rs7593557), c.3048C>T (rs11563208) and c.3174C>G (rs11563071). Results: GC genotype and C allele carriers for SNP c.750G>C were more frequently observed among the group with CAH (χ 2 =9.7, p=0.007). The odds ratio for CAH was estimated to be 3.73 95%CI (1.48; 9.37), p=0.005. Furthermore, GC heterozygotes had a prominent decrease in FEV 1 as compared to GG homozygotes (-12% (-16; -8.1) vs -6.45% (-11; -2.1), p<0.001). GC carriers also had a marked reduction in other spirometric parameters along with FEV 1 . The other SNPs except c.1256G>A showed some tendency to be related to CAH, which, however, was mostly statistically insignificant. Conclusion: GC variant of TRPM8:c.750G>C SNP predisposes to higher risk of CAH in patients with BA, which suggests a potential role of TRPM8 as a novel gene in CAH development.