title: BMP-2 gene polymorphisms and osteoporosis: the Rotterdam Study.
abstract: After reported associations of variations in the BMP-2 gene with osteoporosis in small populations, we studied the association of the BMP-2 gene polymorphisms Ser37Ala and Arg190Ser with osteoporosis in 6353 men and women from the Rotterdam Study. We did not observe an association of these variants with BMD, bone loss, hip structural analysis parameters, and fracture risk.
  
  
  BACKGROUND
  Bone morphogenetic protein 2 (BMP-2) plays a role in osteoblast differentiation. BMP-2 gene variation has previously been associated with osteoporosis in various small populations, but current evidence remains inconclusive about the exact association with osteoporosis. Therefore, we studied the association of two polymorphisms located in the BMP-2 gene (Ser37Ala and Arg190Ser) and haplotypes defined by these polymorphisms with BMD, rates of bone loss, parameters of hip structural analysis (HSA), and fractures in the Rotterdam Study, a large prospective cohort study of diseases in the elderly.
  
  
  METHODS
  Databases were searched for polymorphisms and haplotype blocks in the BMP-2 gene region. Allele frequencies for Ser37Ala and Arg190Ser were determined in 60 blacks and 110 Chinese from Coriell panels. Genotype data on Ser37Ala and Arg190Ser were available for 6353 individuals from the Rotterdam Study population. Haplotype alleles defined by Ser37Ala and Arg190Ser were inferred using PHASE software. Genotype and haplotype analyses for BMD (measured at the lumbar spine and femoral neck), bone loss per year (measured at the femoral neck), and HSA were performed using AN(C)OVA. Fractures were analyzed using a Cox proportional-hazards model and logistic regression. All outcomes were adjusted for age, height, and weight.
  
  
  RESULTS
  Allele frequencies were 2.5% for Ala37 and 40.2% for Ser190, whereas haplotype allele frequencies were 57.28% (Ser37Arg190), 40.19% (Ser37Ser190), 2.50% (Ala37Arg190), and 0.02% (Ala37Ser190). For BMD, bone loss, HSA outcomes, and (incident) fractures, no differences could be seen between genotype and haplotype groups.
  
  
  CONCLUSIONS
  In this large population-based cohort of Dutch whites, we conclude that the BMP-2 Ser37Ala and Arg190Ser polymorphisms or haplotypes thereof are not associated with parameters of osteoporosis.
authors.affiliation: Department of Internal Medicine Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Marco
authors.initials: M
authors.lastname: Medici
authors.forename: Joyce Bj
authors.initials: JB
authors.lastname: van Meurs
authors.forename: Fernando
authors.initials: F
authors.lastname: Rivadeneira
authors.forename: HongYan
authors.initials: H
authors.lastname: Zhao
authors.forename: Pascal P
authors.initials: PP
authors.lastname: Arp
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Huibert Ap
authors.initials: HA
authors.lastname: Pols
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics; D044383:Black People / Q000235:genetics; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D015331:Cohort Studies; D019992:Databases as Topic; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D009426:Netherlands / Q000453:epidemiology; D010024:Osteoporosis / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012307:Risk Factors; D016212:Transforming Growth Factor beta / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta