Association of asthma with β2-adrenergic receptor gene polymorphism and cigarette smoking

Recent studies have suggested that two polymorphisms of the beta (2)-adrenergic receptor (beta (2)AR) gene at codons 16 (arginine to glycine) and 27 (glutamine to glutamate) affect an individual's airway responsiveness, or response to acute or chronic beta (2)-agonist therapy but are not risk factors for asthma. We hypothesize that there is an interaction effect on asthma between the beta (2)AR gene polymorphisms and cigarette smoking. A case-control study was conducted in 128 asthma cases and 136 control individuals identified from 10,014 studied subjects in rural Anqing, China. Allele-specific polymerase chain reaction (PCR) was used to genotype beta (2)AR gene polymorphisms. Multiple logistic regression was used to adjust for potential confounding factors. We found a marginally significant interaction between cigarette smoking and beta (2)AR-16 genotype after adjusting for important confounding factors (p = 0.06). Specifically, we found that compared with never-smoking Gry-16 homozygotes, those ever-smokers who are Arg-16 homozygotes had a significantly increased risk of asthma (odds ratio [OR] = 7.81; 95% confidence interval [CI]: 2.07 to 29.5). This association showed a clear dose-response relationship with the number of cigarettes smoked. However, there was no significant association of asthma with polymorphisms of the beta (2)AR at position 27 (OR = 1.38; 95% CI: 0.69 to 2.73). Our study suggests a gene-environment interaction between the Arg-16 genotype and ever cigarette smoking with respect to the susceptibility of an individual to asthma.