Study objective: β2-Adrenoceptor
Gly16 polymorphism has been associated with asthma severity andβ
2-adrenoceptor receptor downregulation, but not with the
diagnosis of asthma. Glu27 polymorphism may limitβ
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
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