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ß₂-Adrenoceptor Polymorphism and Body Mass Index Are Associated With Adult-Onset Asthma in Sedentary but Not Active Women^*

^* From the Channing Laboratory (Drs. Barr, Speizer, and Camargo) and Division of Pulmonary and Critical Care Medicine (Dr. Drazen), Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, and General Medicine Division (Dr. Barr) and Department of Emergency Medicine (Dr. Camargo), Massachusetts General Hospital, Boston, MA; and Respiratory Center for Children (Dr. Cooper), Children’s Medical Center, Atlantic Health Systems, Morristown, NJ.

Correspondence to: Carlos A. Camargo; Jr, MD, DrPH, FCCP, Channing Laboratory, 181 Longwood Ave, Boston, MA 02115; e-mail: carlos.camargo{at}channing.harvard.edu

Study objective: ß₂-Adrenoceptor Gly16 polymorphism has been associated with asthma severity and ß₂-adrenoceptor receptor downregulation, but not with the diagnosis of asthma. Glu27 polymorphism may limit ß₂-adrenoceptor downregulation and predict body mass index (BMI), particularly among sedentary persons. In addition, BMI predicts asthma. We hypothesized that these DNA sequence variants predict adult-onset asthma only in sedentary women.

Design: Nested case-control study.

Setting: Nurses’ Health Study, a large, prospective cohort study with participants throughout the United States.

Participants: Among lifelong nonsmokers, 171 women with adult-onset, medication-requiring asthma and 137 age-matched control subjects.

Measurements: Physical activity and BMI were self-reported by previously validated questionnaire items. Genomic DNA was obtained from buccal brushings collected via first-class mail.

Results: Of 76 sedentary women, the adjusted odds ratios of Gly16 allele were 7.4 (p = 0.047) for asthma and 13.8 (p = 0.02) for steroid-requiring asthma. No similar associations were observed among 232 active women (p = 0.91). Sedentary individuals with both Gly16 and Glu27 alleles had a less elevated risk for asthma. BMI was associated with asthma and Glu27 allele among sedentary women.

Conclusion: This exploratory analysis suggests an important gene/environment interaction for asthma involving physical activity level. Further study in larger populations is warranted to confirm if sedentary lifestyle unmasks a genetic risk for asthma.

Key Words: asthma • ß₂-adrenoceptor polymorphism • gene/environment interaction • obesity • physical activity

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