Am. J. Respir. Crit. Care Med., Volume 163, Number 6, May 2001, 1404-1409

Association of Asthma with ₂-Adrenergic Receptor Gene Polymorphism and Cigarette Smoking

ZHAOXI WANG, CHANGZHONG CHEN, TIANHUA NIU, DI WU, JIANHUA YANG, BINYAN WANG, ZHIAN FANG, CHANDRI N. YANDAVA, JEFFREY M. DRAZEN, SCOTT T. WEISS, and XIPING XU

Program for Population Genetics, Harvard School of Public Health, Boston, Massachusetts; Channing Laboratory, Department of Medicine, and Pulmonary Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Anhui Meizhong Institute for Biomedical Science and Environmental Health, Anqing, China; Anhui Medical University Institute for Biomedicine, Hefei, China; Beijing Medical University Center for Ecogenetics and Reproductive Health, Beijing, China; and Anqing Public Health Bureau, Anqing, China

Recent studies have suggested that two polymorphisms of the ₂-adrenergic receptor (₂AR) gene at codons 16 (arginine to glycine) and 27 (glutamine to glutamate) affect an individual's airway responsiveness, or response to acute or chronic ₂-agonist therapy but are not risk factors for asthma. We hypothesize that there is an interaction effect on asthma between the ₂AR 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 ₂AR gene polymorphisms. Multiple logistic regression was used to adjust for potential confounding factors. We found a marginally significant interaction between cigarette smoking and ₂AR-16 genotype after adjusting for important confounding factors (p = 0.06). Specifically, we found that compared with never-smoking Gly-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 ₂AR 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.

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