β2-Adrenoceptor polymorphism and body mass index are associated with adult-onset asthma in sedentary but not active women

Study objective: beta (2)-Adrenoceptor Gly16 polymorphism has been associated with asthma severity and beta (2)-adrenoceptor receptor downregulation, but not with the diagnosis of asthma. Glu27 polymorphism may limit beta (2)-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.