Faculty Collaboration Database

Common variants at the PCOL2 and Sp1 binding sites of the COL1A1 gene and their interactive effect influence bone mineral density in Caucasians. J Med Genet 2004 Oct;41(10):752-7

Date

10/07/2004

Pubmed ID

15466008

Pubmed Central ID

PMC1735608

DOI

10.1136/jmg.2004.019851

Scopus ID

2-s2.0-6344239056 (requires institutional sign-in at Scopus site)   44 Citations

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.

Author List

Liu PY, Lu Y, Long JR, Xu FH, Shen H, Recker RR, Deng HW

MESH terms used to index this publication - Major topics in bold

Binding Sites
Bone Density
Bone and Bones
Collagen Type I
Female
Genetic Variation
Genotype
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide
Response Elements
Sp1 Transcription Factor