Calcified Tissue International

, Volume 83, Issue 3, pp 155–166

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

Authors

    • CPMC Research Institute
    • California Pacific Medical Center Research Institute, San Francisco Coordinating Center UCSF
  • Brent C. Taylor
    • Center for Chronic Disease Outcomes ResearchMinneapolis VA Medical Center
    • Division of Epidemiology and Community HealthUniversity of Minnesota
  • Li-Yung Lui
    • CPMC Research Institute
  • Joseph M. Zmuda
    • Department of EpidemiologyUniversity of Pittsburgh
  • Jane A. Cauley
    • Department of EpidemiologyUniversity of Pittsburgh
  • Kristine E. Ensrud
    • Center for Chronic Disease Outcomes ResearchMinneapolis VA Medical Center
    • Division of Epidemiology and Community HealthUniversity of Minnesota
    • Department of MedicineUniversity of Minnesota
  • Teresa A. Hillier
    • Kaiser Permanente Center for Health Research Northwest/Hawaii
  • Marc C. Hochberg
    • Department of Medicine and Epidemiology and Preventative MedicineUniversity of Maryland School of Medicine University
  • Jia Li
    • Department of Human GeneticsRoche Molecular Systems
  • Brian K. Rhees
    • Department of Human GeneticsRoche Molecular Systems
  • Henry A. Erlich
    • Department of Human GeneticsRoche Molecular Systems
  • Mark D. Sternlicht
    • Department of AnatomyUniversity of California
  • Gary Peltz
    • Department of Genetics and GenomicsRoche Palo Alto
  • Steven R. Cummings
    • CPMC Research Institute
    • Department of EpidemiologyUniversity of California
  • For the Study of Osteoporotic Fractures (SOF) Research Group
Article

DOI: 10.1007/s00223-008-9165-y

Cite this article as:
Tranah, G.J., Taylor, B.C., Lui, L. et al. Calcif Tissue Int (2008) 83: 155. doi:10.1007/s00223-008-9165-y

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.

Keywords

Genetics Polymorphism Osteoporosis BMD Fracture

Copyright information

© Springer Science+Business Media, LLC 2008