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J Med Genet 41:752-757 doi:10.1136/jmg.2004.019851
  • Original article

Common variants at the PCOL2 and Sp1 binding sites of the COL1A1 gene and their interactive effect influence bone mineral density in Caucasians

  1. P-Y Liu1,
  2. Y Lu1,
  3. J-R Long1,
  4. F-H Xu1,2,
  5. H Shen1,2,
  6. R R Recker1,
  7. H-W Deng1,2,3
  1. 1Osteoporosis Research Center, Creighton University, Omaha, NE 68131, USA
  2. 2Department of Biomedical Sciences, Creighton University, Omaha, NE 68131, USA
  3. 3Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China
  1. Correspondence to:
 Dr H-W Deng
 Osteoporosis Research Center, Creighton University Medical Center, 601 N. 30th St., Suite 6787, Omaha, NE 68131, USA; dengcreighton.edu
  • Received 22 March 2004
  • Accepted 17 April 2004

Abstract

Background: Osteoporosis, mainly characterised by low bone mineral density (BMD), is a serious public health problem. The collagen type I alpha 1 (COL1A1) gene is a prominent candidate gene for osteoporosis. Here, we examined whether genetic variants at the COL1A1 gene can influence BMD variation.

Methods: BMD was measured at nine skeletal sites in 313 Caucasian males and 308 Caucasian females. We screened four single nucleotide polymorphisms (SNPs) at the COL1A1 gene: PCOL2 (-1997 G/T) in the promoter, Sp1 (1546 G/T) in the intron 1, Gly19Cys (3911 G/A) in exon 8, and Ala897Thr (13 773 G/A) in exon 45. Univariate and multivariate association approaches were used in the analyses.

Results: In multivariate analyses, we found a strong association between the PCOL2 SNP and BMD (p = 0.007 to 0.024) and a suggestive association between the Sp1 SNP and BMD (p = 0.023 to 0.048) in elderly Caucasian females. Interestingly, the interaction of these two SNPs was highly significantly associated with BMD variation (p = 0.001 to 0.003). The haplotype GG at the two SNPs had, on average, 2.7% higher BMD than non-carriers (p = 0.006 to 0.026).

Conclusions: Our data suggested that the common genetic variants at the PCOL2 and Sp1 sites, and importantly, their interactive effects, may contribute to BMD variation in elderly Caucasian females. Further studies are necessary to delineate the mechanisms underlying the effects of these common variants on BMD variation and to test their clinical relevance for general populations. In addition, our study highlighted the importance of multivariate analyses when multiple correlated phenotypes are under study.

Footnotes

  • The study was partially supported by grants from the Health Future Foundation, NIH and the State of Nebraska. The study was also benefited by grants from CNSF, the Huo Ying Dong Education Foundation, and the Ministry of Education of China.

  • Conflict of interest: none declared.