Calcified Tissue International

, Volume 84, Issue 2, pp 85–96

Haplotypes of Promoter and Intron 1 Polymorphisms in the COLIA1 Gene Are Associated with Increased Risk of Osteoporosis

  • L. B. Husted
  • T. Harsløf
  • N. Gonzalez-Bofill
  • A. Schmitz
  • M. Carstens
  • L. Stenkjær
  • B. L. Langdahl
Article

DOI: 10.1007/s00223-008-9199-1

Cite this article as:
Husted, L.B., Harsløf, T., Gonzalez-Bofill, N. et al. Calcif Tissue Int (2009) 84: 85. doi:10.1007/s00223-008-9199-1

Abstract

Osteoporosis is a common age-related disease with a strong genetic influence. COLIA1 is one of the most extensively studied candidate genes and has consistently been associated with BMD and fracture. We examined the effects of the polymorphisms –1997G>T, –1663indelT, and +1245G>T and their haplotypes on vertebral fractures and bone mineral density (BMD) in a case-control study comprising 462 osteoporotic patients and 336 controls. The −1663indelT polymorphism was associated with a decreased lumbar spine (ls) BMD, 0.75 ± 0.14 g/cm2, in individuals with the del/del genotype versus 0.83 ± 0.18 and 0.85 ± 0.18 g/cm2 in individuals with the ins/del and ins/ins genotypes, respectively (p = 0.02). The T-allele of the +1245G>T polymorphism, which was in strong linkage disequilibrium (LD) with –1663indelT, was also associated with a decreased lsBMD (p = 0.02). –1997G>T was not significantly associated with lsBMD. The three most common haplotypes accounted for 98.5% of the alleles. Individuals with one or two copies of haplotype 1 (–1997G/–1663ins/+1245G) had a significantly higher lsBMD, 0.84 ± 0.18 and 0.85 ± 0.15 g/cm2, respectively, versus 0.78 ± 0.15 g/cm2 in noncarriers (p = 0.01). Individuals with two copies of haplotype 2 (–1997G/–1663del/+1245T) had a significantly lower lsBMD, 0.76 ± 0.14 g/cm2, versus 0.85 ± 0.18 and 0.82 ± 0.18 g/cm2, respectively, in individuals with zero or one copy (p = 0.03). The odds ratio for vertebral fracture in individuals carrying the variant T-allele of the –1997G>T polymorphism was 1.49 (CI, 1.03–2.16; p = 0.03). Logistic regression revealed that this effect was partly independent of BMD. In conclusion, the −1663del and +1245T alleles influence BMD negatively, whereas the –1997T-allele has a minor effect on BMD but increases the risk of vertebral fractures. These findings are in agreement with functional studies showing that these polymorphisms influence gene expression.

Keywords

CollagenFracture riskBMDPolymorphisms

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • L. B. Husted
    • 1
  • T. Harsløf
    • 1
  • N. Gonzalez-Bofill
    • 1
  • A. Schmitz
    • 2
  • M. Carstens
    • 1
  • L. Stenkjær
    • 1
  • B. L. Langdahl
    • 1
  1. 1.Department of Endocrinology and MetabolismAarhus University HospitalAarhus CDenmark
  2. 2.Department of Internal MedicineVejle SygehusVejleDenmark