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Genetic Variation in Candidate Osteoporosis Genes, Bone Mineral Density, and Fracture Risk: The Study of Osteoporotic Fractures

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Abstract

Candidate osteoporosis gene variants were examined for associations with fracture risk and bone mineral density (BMD). A total of 9704 white women were recruited at four U.S. clinical centers and enrolled into the Study of Osteoporotic Fractures, a longitudinal cohort study. Genotyping of 31 polymorphisms from 18 candidate osteoporosis genes was performed in 6752 women. Incident radiographic fractures were identified at the third and eighth examinations compared with the baseline examination. BMD was measured at the total hip by dual-energy X-ray absorptiometry. Analyses were adjusted for age, clinic site, and self-reported ethnicity. During a mean follow-up of 14.5 years, a total of 849 hip, 658 vertebral, and 2496 nonhip/nonvertebral fractures occurred in 6752 women. Women carrying the ALOX15_G48924T T/T genotype had a higher rate of hip fracture (hazard ratio [HR] = 1.33;95% confidence interval [95% CI] = 1.00–1.77) compared with the G/G genotype. Compared with those carrying the PRL_T228C T/T genotype, women with either the C/C (HR = 0.80; 95% CI = 0.67–0.95) or C/T (HR = 0.81; 95% CI = 0.68–0.97) genotype had a lower rate of nonvertebral/nonhip fractures. Women carrying the BMP2_A125611G G/G genotype had a higher rate of vertebral fracture (odds ratio [OR] = 1.51; 95% CI = 1.03–2.23) compared with the A/A genotype. Women with the ESR1_C1335G G/G genotype had a higher rate of vertebral fracture (OR = 1.64; 95% CI = 1.07–2.50) compared with the C/C genotype. Compared with those with the MMP2_C595T C/C genotype, women with the C/T (OR = 0.79; 95% CI = 0.65–0.96) or T/T (OR = 0.44; 95% CI = 0.27–0.72) genotype had a lower rate of vertebral fracture. In conclusion, polymorphisms in several candidate genes were associated with hip, vertebral, and nonhip/nonvertebral fractures but not with total hip BMD in this large population based cohort study.

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Acknowledgments

Supported by NIH grants AG05407, AR35582, AG05394, AR35584, AR35583, AR46238, AG005407, AG027576-22, AG005394-22A1, and AG027574-22A1. J. A. Cauley receives funding from Merck & Company, Eli Lily & Company, Pfizer Pharmaceuticals, and Novartis Pharmaceuticals. K. E. Ensrud is a federal employee of the Veterans Affairs Medical Center in Minneapolis, Minnesota, and has received research support from California Pacific Medical Center, who receives funding from Roche Molecular Systems. M. C. Hochberg acts as a consultant for Amgen. J. Li, B. Rhees, and H. Erlich are all employees of Roche Molecular Systems, which provided genotyping reagents and services for this study at no cost under a research collaboration. G. Peltz is a former employee of Roche Palo Alto. S. Cummings, L. Lui, and G. Tranah are employees of the California Pacific Medical Center and receive research support from Roche Molecular Systems.

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Authors and Affiliations

  1. CPMC Research Institute, San Francisco, CA, 94120, USA

    Gregory J. Tranah, Li-Yung Lui & Steven R. Cummings

  2. California Pacific Medical Center Research Institute, San Francisco Coordinating Center UCSF, 185 Berry Street, Lobby 4, Suite 5700, San Francisco, CA, 94107-1728, USA

    Gregory J. Tranah

  3. Center for Chronic Disease Outcomes Research, Minneapolis VA Medical Center, Minneapolis, MN, 55417, USA

    Brent C. Taylor & Kristine E. Ensrud

  4. Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, 55455, USA

    Brent C. Taylor & Kristine E. Ensrud

  5. Department of Epidemiology, University of Pittsburgh, Pittsburg, PA, 15261, USA

    Joseph M. Zmuda & Jane A. Cauley

  6. Department of Medicine, University of Minnesota, Minneapolis, MN, 55455, USA

    Kristine E. Ensrud

  7. Kaiser Permanente Center for Health Research Northwest/Hawaii, Portland, OR, 97227, USA

    Teresa A. Hillier

  8. Department of Medicine and Epidemiology and Preventative Medicine, University of Maryland School of Medicine University, Baltimore, MD, 21201, USA

    Marc C. Hochberg

  9. Department of Human Genetics, Roche Molecular Systems, Alameda, CA, 94501-1145, USA

    Jia Li, Brian K. Rhees & Henry A. Erlich

  10. Department of Anatomy, University of California, San Francisco, CA, 94107, USA

    Mark D. Sternlicht

  11. Department of Genetics and Genomics, Roche Palo Alto, Palo Alto, CA, 94304, USA

    Gary Peltz

  12. Department of Epidemiology, University of California, San Francisco, CA, 94107, USA

    Steven R. Cummings

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  1. Gregory J. Tranah
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  2. Brent C. Taylor
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For the Study of Osteoporotic Fractures (SOF) Research Group

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Correspondence to Gregory J. Tranah.

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Tranah, G.J., Taylor, B.C., Lui, LY. et al. Genetic Variation in Candidate Osteoporosis Genes, Bone Mineral Density, and Fracture Risk: The Study of Osteoporotic Fractures. Calcif Tissue Int 83, 155–166 (2008). https://doi.org/10.1007/s00223-008-9165-y

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