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The -1997 G/T and Sp1 Polymorphisms in the Collagen Type I alpha1 ( COLIA1) Gene in Relation to Changes in Femoral Neck Bone Mineral Density and the Risk of Fracture in the Elderly: The Rotterdam Study.
- Source :
- Calcified Tissue International; Jul2007, Vol. 81 Issue 1, p18-25, 8p, 1 Diagram, 4 Charts
- Publication Year :
- 2007
-
Abstract
- The COLIA1 Sp1 polymorphism has been associated with bone mineral density (BMD) and fracture. A promoter polymorphism, -1997 G/T, also has been associated with BMD. In this study, we examined whether these polymorphisms alone and in the form of haplotypes influence bone parameters and fracture risk in a large population-based cohort of elderly Caucasians. We determined the COLIA1 -1997 G/T (promoter) and Sp1 G/T (intron) polymorphisms in 6,280 individuals and inferred haplotypes. Femoral neck BMD and BMD change were compared across COLIA1 genotypes at baseline and follow-up (mean 6.5 years). We also investigated the relationship between the COLIA1 polymorphisms and incident nonvertebral fractures, which were recorded during a mean follow-up period of 7.4 years. Vertebral fractures were assessed by radiographs on 3,456 genotyped individuals. Femoral neck BMD measured at baseline was 3.8% lower in women carrying two copies of the T-Sp1 allele ( P for trend = 0.03). No genotype dependent differences in BMD loss were observed. In women homozygous for the T allele of the Sp1 polymorphism, the risk of fragility fracture increased 2.3 times (95% confidence interval 1.4–3.9, P = 0.001). No such association was observed with the promoter polymorphism. In men, no association with either the Sp1 or the -1997 G/T promoter polymorphism was seen with BMD or fracture. High linkage disequilibrium (LD; D′ = 0.99, r <superscript>2 </superscript>= 0.03) exists between the two studied polymorphisms. We observed three haplotypes in our population: haplotype 1 (G<subscript>promoter</subscript>–G<subscript>intron</subscript>) frequency (f) = 69%, haplotype 2 (G<subscript>promoter</subscript>–T<subscript>intron</subscript>) f = 17.6%, and haplotype 3 (T<subscript>promoter</subscript>–G<subscript>intron</subscript>) f = 13.4%. Haplotype 2 was associated with a 2.1-fold increased risk of fragility fracture in women (95% confidence interval 1.2–3.7, P = 0.001). We confirm that the COLIA1 Sp1 polymorphism influences BMD and the risk of fracture in postmenopausal Caucasian women. In contrast, we found no independent effect of the -1997 G/T promoter polymorphism on BMD or fracture. [ABSTRACT FROM AUTHOR]
- Subjects :
- FEMUR neck
COLLAGEN
GENES
GENETIC polymorphisms
BONE fractures
OLDER people
Subjects
Details
- Language :
- English
- ISSN :
- 0171967X
- Volume :
- 81
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Calcified Tissue International
- Publication Type :
- Academic Journal
- Accession number :
- 25602909
- Full Text :
- https://doi.org/10.1007/s00223-007-9033-1