Transient receptor potential melastatin 8 gene polymorphism is associated with cold-induced airway hyperresponsiveness in bronchial asthma.
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.
Laboratory of Prophylaxis of Nonspecific Lung Diseases, Far Eastern Scientific Centre of Physiology and Pathology of Respiration, Blagoveshchensk, Russia.
Denis E
http://orcid.org/0000-0003-3921-8755
DE
Naumov
Laboratory of Functional Research of Respiratory System, Far Eastern Scientific Centre of Physiology and Pathology of Respiration, Blagoveshchensk, Russia.
Juliy M
JM
Perelman
Laboratory of Prophylaxis of Nonspecific Lung Diseases, Far Eastern Scientific Centre of Physiology and Pathology of Respiration, Blagoveshchensk, Russia.
Victor P
VP
Kolosov
Laboratory of Human Molecular Genetics, Research Institute of Internal and Preventive Medicine, Novosibirsk, Russia.
Tatyana A
TA
Potapova
Laboratory of Human Molecular Genetics, Research Institute of Internal and Preventive Medicine, Novosibirsk, Russia.
Vladimir N
VN
Maksimov
Department of Respiratory Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Xiangdong
X
Zhou
D000328:Adult; D001249:Asthma / Q000150:complications / Q000503:physiopathology*; D003080:Cold Temperature / Q000009:adverse effects*; D005260:Female; D005541:Forced Expiratory Volume; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006985:Hyperventilation / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D012150:Polymorphism, Restriction Fragment Length; D013147:Spirometry; D050053:TRPM Cation Channels / Q000235:genetics*
D050053:TRPM Cation Channels; C425966:TRPM8 protein, human
asthma; cold temperature; polymorphism; spirometry; transient receptor potential channel