Transient receptor potential melastatin 8 gene polymorphism is associated with cold‐induced airway hyperresponsiveness in bronchial asthma

Background and objective Cold‐induced airway hyperresponsiveness ( CAH ) is common in bronchial asthma ( BA ) patients and represents a problem for those living in cold climate. Transient receptor potential melastatin 8 ( TRPM 8) channel is the main cold temperature sensor in humans that could mediate cold response in asthmatics with CAH . No associations between TRPM8 gene polymorphisms and CAH have been reported. Methods The present study involved 123 BA patients. CAH was assessed by 3‐min isocapnic (5% CO 2 ) cold air (−20°C) hyperventilation challenge. The c.750G >  C (rs11562975), c.1256G >  A (rs7593557), c.3048C >  T (rs11563208) and c.3174C >  G (rs11563071) polymorphisms of TRPM8 gene were genotyped by allele‐specific polymerase chain reaction (PCR) and PCR with subsequent restriction fragment length polymorphism analysis. Results : GC genotype and C allele carriers of the c.750G >  C (rs11562975) polymorphism were more frequently observed to exhibit CAH . The estimated odds ratio for the GC genotype was 3.73 95% CI (1.48; 9.37), P  = 0.005. Furthermore, GC heterozygotes had a prominent decrease in forced expiratory volume in 1 s after the challenge 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. Conclusions The GC variant of the TRPM8 :c.750G >  C (rs11562975) polymorphism is associated with CAH in patients with BA , which suggests a potential role of TRPM8 in CAH development.