Abstract
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 (χ2=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 FEV1 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 FEV1. 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.
- © 2013 ERS