PLoS Medicine (Apr 2006)

Large-scale evidence for the effect of the COLIA1 Sp1 polymorphism on osteoporosis outcomes: the GENOMOS study.

  • Stuart H Ralston,
  • André G Uitterlinden,
  • Maria Luisa Brandi,
  • Susana Balcells,
  • Bente L Langdahl,
  • Paul Lips,
  • Roman Lorenc,
  • Barbara Obermayer-Pietsch,
  • Serena Scollen,
  • Mariona Bustamante,
  • Lise Bjerre Husted,
  • Alisoun H Carey,
  • Adolfo Diez-Perez,
  • Alison M Dunning,
  • Alberto Falchetti,
  • Elzbieta Karczmarewicz,
  • Marcin Kruk,
  • Johannes P T M van Leeuwen,
  • Joyce B J van Meurs,
  • Jon Mangion,
  • Fiona E A McGuigan,
  • Leonardo Mellibovsky,
  • Francesca del Monte,
  • Huibert A P Pols,
  • Jonathan Reeve,
  • David M Reid,
  • Wilfried Renner,
  • Fernando Rivadeneira,
  • Natasja M van Schoor,
  • Rachael E Sherlock,
  • John P A Ioannidis,
  • GENOMOS Investigators

DOI
https://doi.org/10.1371/journal.pmed.0030090
Journal volume & issue
Vol. 3, no. 4
p. e90

Abstract

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BackgroundOsteoporosis and fracture risk are considered to be under genetic control. Extensive work is being performed to identify the exact genetic variants that determine this risk. Previous work has suggested that a G/T polymorphism affecting an Sp1 binding site in the COLIA1 gene is a genetic marker for low bone mineral density (BMD) and osteoporotic fracture, but there have been no very-large-scale studies of COLIA1 alleles in relation to these phenotypes.Methods and findingsHere we evaluated the role of COLIA1 Sp1 alleles as a predictor of BMD and fracture in a multicenter study involving 20,786 individuals from several European countries. At the femoral neck, the average (95% confidence interval [CI]) BMD values were 25 mg/cm2 (CI, 16 to 34 mg/cm2) lower in TT homozygotes than the other genotype groups (p ConclusionsAllowing for the inevitable heterogeneity between participating teams, this study-which to our knowledge is the largest ever performed in the field of osteoporosis genetics for a single gene-demonstrates that the COLIA1 Sp1 polymorphism is associated with reduced BMD and could predispose to incident vertebral fractures in women, independent of BMD. The associations we observed were modest however, demonstrating the importance of conducting studies that are adequately powered to detect and quantify the effects of common genetic variants on complex diseases.