Beta(2)-adrenoceptor polymorphism and body mass index are associated with adult-onset asthma in sedentary but not active women.
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.
Barr
R G
RG
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Cooper
D M
DM
Speizer
F E
FE
Drazen
J M
JM
Camargo
C A
CA
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*
D018343:Receptors, Adrenergic, beta-2