Beta(2)-adrenoceptor polymorphism and body mass index are associated with adult-onset asthma in sedentary but not active women

Chest. 2001 Nov;120(5):1474-9. doi: 10.1378/chest.120.5.1474.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Age of Onset
  • Asthma / etiology*
  • Asthma / genetics
  • Body Mass Index*
  • Exercise*
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Life Style
  • Middle Aged
  • Point Mutation
  • Polymorphism, Genetic*
  • Receptors, Adrenergic, beta-2 / genetics*


  • Receptors, Adrenergic, beta-2