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

Respirology. 2015 Nov;20(8):1192-7. doi: 10.1111/resp.12605. Epub 2015 Aug 13.

Abstract

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 (TRPM8) 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% CO2 ) 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.

Keywords: asthma; cold temperature; polymorphism; spirometry; transient receptor potential channel.

MeSH terms

  • Adult
  • Asthma / complications
  • Asthma / physiopathology*
  • Cold Temperature / adverse effects*
  • Female
  • Forced Expiratory Volume
  • Genotype
  • Heterozygote
  • Homozygote
  • Humans
  • Hyperventilation / etiology
  • Hyperventilation / genetics*
  • Hyperventilation / physiopathology
  • Male
  • Polymorphism, Restriction Fragment Length
  • Spirometry
  • TRPM Cation Channels / genetics*

Substances

  • TRPM Cation Channels
  • TRPM8 protein, human