title: Large-scale analysis of association between polymorphisms in the transforming growth factor beta 1 gene (TGFB1) and osteoporosis: the GENOMOS study.
abstract: BACKGROUND
  The TGFB1 gene which encodes transforming growth factor beta 1, is a strong candidate for susceptibility to osteoporosis and several studies have reported associations between bone mineral density (BMD), osteoporotic fractures and polymorphisms of TGFB1, although these studies have yielded conflicting results.
  
  
  METHODS
  We investigated associations between TGFB1 polymorphisms and BMD and fracture in the GENOMOS study: a prospective multicenter study involving 10 European research studies including a total of 28,924 participants. Genotyping was conducted for known TGFB1 polymorphisms at the following sites: G-1639-A (G-800-A, rs1800468), C-1348-T (C-509-T, rs1800469), T29-C (Leu10Pro, rs1982073), G74-C (Arg25Pro, rs1800471) and C788-T (Thr263Ile, rs1800472). These polymorphisms were genotyped prospectively and methodology was standardized across research centers. Genotypes and haplotypes were related to BMD at the lumbar sine and femoral neck and fractures.
  
  
  RESULTS
  There were no significant differences in either women or men at either skeletal site for any of the examined polymorphisms with the possible exception of a weak association with reduced BMD (-12 mg/cm2) in men with the T-1348 allele (p<0.05). None of the haplotypes was associated with BMD and none of the polymorphisms or haplotypes significantly affected overall risk of fractures, however, the odds ratio for incident vertebral fracture in carriers of the rare T788 allele was 1.64 (95% CI: 1.09-2.64), p<0.05.
  
  
  CONCLUSIONS
  This study indicates that polymorphic variation in the TGFB1 gene does not play a major role in regulating BMD or susceptibility to fractures. The weak associations we observed between the C-1348-T and lumbar spine BMD in men and between C788-T and risk of incident vertebral fractures are of interest but could be chance findings and will need replication in future studies.
authors.affiliation: Department of Endocrinology, Aarhus University Hospital, Aarhus, Denmark. bente.langdahl@as.aaa.dk
authors.forename: Bente L
authors.initials: BL
authors.lastname: Langdahl
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: Stuart H
authors.initials: SH
authors.lastname: Ralston
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Trikalinos
authors.forename: Susanne
authors.initials: S
authors.lastname: Balcells
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Brandi
authors.forename: Serena
authors.initials: S
authors.lastname: Scollen
authors.forename: Paul
authors.initials: P
authors.lastname: Lips
authors.forename: Roman
authors.initials: R
authors.lastname: Lorenc
authors.forename: Barbara
authors.initials: B
authors.lastname: Obermayer-Pietsch
authors.forename: David M
authors.initials: DM
authors.lastname: Reid
authors.forename: Jácome Bruges
authors.initials: JB
authors.lastname: Armas
authors.forename: Pascal P
authors.initials: PP
authors.lastname: Arp
authors.forename: Amelia
authors.initials: A
authors.lastname: Bassiti
authors.forename: Mariona
authors.initials: M
authors.lastname: Bustamante
authors.forename: Lise Bjerre
authors.initials: LB
authors.lastname: Husted
authors.forename: Alison H
authors.initials: AH
authors.lastname: Carey
authors.forename: Ramon
authors.initials: R
authors.lastname: Pérez Cano
authors.forename: Harald
authors.initials: H
authors.lastname: Dobnig
authors.forename: Alison M
authors.initials: AM
authors.lastname: Dunning
authors.forename: Astrid
authors.initials: A
authors.lastname: Fahrleitner-Pammer
authors.forename: Alberto
authors.initials: A
authors.lastname: Falchetti
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Karczmarewicz
authors.forename: Marcin
authors.initials: M
authors.lastname: Kruk
authors.forename: Johannes P T M
authors.initials: JP
authors.lastname: van Leeuwen
authors.forename: Laura
authors.initials: L
authors.lastname: Masi
authors.forename: Joyce B J
authors.initials: JB
authors.lastname: van Meurs
authors.forename: Jon
authors.initials: J
authors.lastname: Mangion
authors.forename: Fiona E A
authors.initials: FE
authors.lastname: McGuigan
authors.forename: Leonardo
authors.initials: L
authors.lastname: Mellibovsky
authors.forename: Leif
authors.initials: L
authors.lastname: Mosekilde
authors.forename: Xavier
authors.initials: X
authors.lastname: Nogués
authors.forename: Huibert A P
authors.initials: HA
authors.lastname: Pols
authors.forename: Jonathan
authors.initials: J
authors.lastname: Reeve
authors.forename: Wilfried
authors.initials: W
authors.lastname: Renner
authors.forename: Fernando
authors.initials: F
authors.lastname: Rivadeneira
authors.forename: Natasja M
authors.initials: NM
authors.lastname: van Schoor
authors.forename: John P A
authors.initials: JP
authors.lastname: Ioannidis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density; D016022:Case-Control Studies; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D005272:Femur Neck / Q000378:metabolism; D050723:Fractures, Bone / Q000235:genetics; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008159:Lumbar Vertebrae / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010024:Osteoporosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors; D016103:Spinal Fractures / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
chemical_list: D053773:Transforming Growth Factor beta1