PT  - JOURNAL ARTICLE
AU  - Denis E. Naumov
AU  - Julius M. Perelman
AU  - Vladimir N. Maksimov
AU  - Viktor P. Kolosov
AU  - Xiandong Zhou
AU  - Qi Li
TI  - Effect of <em>ADRB2</em> polymorphism on the airway response to cold air in asthmatics
DP  - 2011 Sep 01
TA  - European Respiratory Journal
PG  - p440
VI  - 38
IP  - Suppl 55
4099  - http://erj.ersjournals.com/content/38/Suppl_55/p440.short
4100  - http://erj.ersjournals.com/content/38/Suppl_55/p440.full
SO  - Eur Respir J2011 Sep 01; 38
AB  - Background: Previously we've found out that the decline in β2-adrenoreceptors (β2-AR) function affects airway response to cold air.Objective: The aim of our study was to reveal the contribution of Arg16Gly SNP (rs1042713) in the development of cold airway hyperresponsiveness (CAHR) in asthmatics.Methods: The study included examination of 60 mild to moderate asthmatics of Caucasian race, mostly non-smokers (mean age 36±1.39). All the patients underwent spirometry before and after the challenge with 3-minute isocapnic (5% CO2) cold air (-20°C) hyperventilation (ICAH). More than 10% drop in FEV1 was interpreted as a positive result. Intracellular cyclic adenosine monophosphate (cAMP) concentration in lymphocytes was measured before and 30 min after ICAH under in vitro stimulation with 10-6M epinephrine. PCR-RFLP analysis was used for genotyping.Results: Arg16Arg genotype dominated in the group with CAHR (χ2=7.47; p=0.02). Mean FEV1 drop differed between homozygous patients (16.03±2.07 in Arg16 vs. 8.66±1.12 in Gly16, p=0.0045). cAMP concentration didn't depend on genotype before the challenge, but 30 min after there was a significant fall in cells ability to produce cAMP in subjects with Arg16Arg genotype (p=0.03). Moreover, Arg16 homozygotes had lower cAMP level as compared to Gly16 (48 (32.8; 61.6) and 78 (59.9; 81.3) pM/106cells, respectively; p=0.0048).Conclusions: These data suggest a definite proof for contribution of primary β2-AR dysfunction into the development of CAHR in our population sample. CAHR was strongly associated with Arg16Arg genotype. Blunted cAMP response in Arg16Arg subjects indicates inherited predisposition of their β2-AR to acute desensitization during the ICAH.