title: Beta(2)-adrenoceptor polymorphism and body mass index are associated with adult-onset asthma in sedentary but not active women.
abstract: 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.
  
  
  METHODS
  Nested case-control study.
  
  
  METHODS
  Nurses' Health Study, a large, prospective cohort study with participants throughout the United States.
  
  
  METHODS
  Among lifelong nonsmokers, 171 women with adult-onset, medication-requiring asthma and 137 age-matched control subjects.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: R G
authors.initials: RG
authors.lastname: Barr
authors.forename: D M
authors.initials: DM
authors.lastname: Cooper
authors.forename: F E
authors.initials: FE
authors.lastname: Speizer
authors.forename: J M
authors.initials: JM
authors.lastname: Drazen
authors.forename: C A
authors.initials: CA
authors.lastname: Camargo
mesh_terms: D000328:Adult; D017668:Age of Onset; D001249:Asthma / Q000209:etiology* / Q000235:genetics; D015992:Body Mass Index; D015444:Exercise; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008019:Life Style; D008875:Middle Aged; D017354:Point Mutation; D011110:Polymorphism, Genetic; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*
chemical_list: D018343:Receptors, Adrenergic, beta-2