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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

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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 2 = 0.03) exists between the two studied polymorphisms. We observed three haplotypes in our population: haplotype 1 (Gpromoter–Gintron) frequency (f) = 69%, haplotype 2 (Gpromoter–Tintron) f = 17.6%, and haplotype 3 (Tpromoter–Gintron) 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.

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Acknowledgement

We thank B. Basdew and W. Hugens for help in genotyping and data management. This work was supported by the Netherlands Organization for Scientific Research (014–93–015) and the European GENOMOS project (QL46-CT-2002–02629) and was part of N. Y.’s MSc Training Program in Genetic Epidemiology at the Netherlands Institute for Health Sciences.

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Authors and Affiliations

  1. Netherlands Institute for Health Science, Rotterdam, The Netherlands

    Nahid Yazdanpanah

  2. Department of Internal Medicine, Erasmus Medical Center, P.O. Box 2040, 3000, CA, Rotterdam, The Netherlands

    Nahid Yazdanpanah, Fernando Rivadeneira, Joyce B. J. van Meurs, M. Carola Zillikens, P. Arp, Huibert A. P. Pols & André G. Uitterlinden

  3. Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands

    Nahid Yazdanpanah, Fernando Rivadeneira, Albert Hofman, Cornelia M. van Duijn, Huibert A. P. Pols & André G. Uitterlinden

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  1. Nahid Yazdanpanah
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  2. Fernando Rivadeneira
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  3. Joyce B. J. van Meurs
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  9. André G. Uitterlinden
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Correspondence to André G. Uitterlinden.

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Yazdanpanah, N., Rivadeneira, F., van Meurs, J.B.J. et al. 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. Calcif Tissue Int 81, 18–25 (2007). https://doi.org/10.1007/s00223-007-9033-1

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  • DOI: https://doi.org/10.1007/s00223-007-9033-1

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