title: Association of polymorphisms in the beta-2 adrenergic receptor gene with fracture risk and bone mineral density.
abstract: Signaling through the beta-2 adrenergic receptor (B2AR) on the osteoblast influences bone remodeling in rodents. In the B2AR gene, three polymorphisms influence receptor function. We show that these polymorphisms are not associated with fracture risk or bone mineral density in the UCP, Rotterdam Study, and GEFOS cohorts.
  
  
  BACKGROUND
  Signaling through the beta-2 adrenergic receptor (B2AR) on the osteoblast influences bone remodeling in rodents. In the B2AR gene, three polymorphisms are known to influence receptor function in vitro and in vivo (rs1042713, rs1042714, and rs1800888). We examined the role of these polymorphisms in the B2AR gene on human bone metabolism.
  
  
  METHODS
  We performed nested case-control studies to determine the association of these polymorphisms with fracture risk in the Utrecht Cardiovascular Pharmacogenetics (UCP) cohort and in three cohorts of the Rotterdam Study. We also determined the association of these polymorphisms with bone mineral density (BMD) in the GEFOS Consortium. UCP contains drug-dispensing histories from community pharmacies linked to national registrations of hospital discharges in the Netherlands. The Rotterdam Study is a prospective cohort study investigating demographics and risk factors of chronic diseases. GEFOS is a large international collaboration studying the genetics of osteoporosis. Fractures were defined by ICD-9 codes 800-829 in the UCP cohort (158 cases and 2617 unmatched controls) and by regular X-ray examinations, general practitioner, and hospital records in the Rotterdam Study (2209 cases and 8559 unmatched controls). BMD was measured at the femoral neck and lumbar spine using dual-energy X-ray absorptiometry in GEFOS (N = 32,961).
  
  
  RESULTS
  Meta-analysis of the two nested case-control studies showed pooled odds ratios of 0.98 (0.91-1.05, p = 0.52), 1.04 (0.97-1.12, p = 0.28), and 1.16 (0.83-1.62, p = 0.38) for the associations between rs1042713, rs1042714, and rs1800888 per minor allele and fractures, respectively. There were no significant associations of the polymorphisms and BMD in GEFOS.
  
  
  CONCLUSIONS
  In conclusion, polymorphisms in the beta-2 adrenergic receptor gene are not associated with fracture risk or BMD.
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, P.O. Box 22660, 1100 DD, Amsterdam, The Netherlands.
authors.forename: A G
authors.initials: AG
authors.lastname: Veldhuis-Vlug
authors.forename: L
authors.initials: L
authors.lastname: Oei
authors.forename: P C
authors.initials: PC
authors.lastname: Souverein
authors.forename: M W T
authors.initials: MW
authors.lastname: Tanck
authors.forename: F
authors.initials: F
authors.lastname: Rivadeneira
authors.forename: M C
authors.initials: MC
authors.lastname: Zillikens
authors.forename: P W
authors.initials: PW
authors.lastname: Kamphuisen
authors.forename: A H
authors.initials: AH
authors.lastname: Maitland-van der Zee
authors.forename: M C H
authors.initials: MC
authors.lastname: de Groot
authors.forename: A
authors.initials: A
authors.lastname: Hofman
authors.forename: A G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: E
authors.initials: E
authors.lastname: Fliers
authors.forename: A
authors.initials: A
authors.lastname: de Boer
authors.forename: P H
authors.initials: PH
authors.lastname: Bisschop
mesh_terms: D000368:Aged; D015519:Bone Density / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008498:Medical Record Linkage; D008875:Middle Aged; D010024:Osteoporosis / Q000235:genetics; D058866:Osteoporotic Fractures / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*
chemical_list: D018343:Receptors, Adrenergic, beta-2