Effect of ADRB2 polymorphism on the airway response to cold air in asthmatics

Abstract

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.