Calcified Tissue International

, Volume 83, Issue 3, pp 155–166 | Cite as

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

  • Gregory J. Tranah
  • Brent C. Taylor
  • Li-Yung Lui
  • Joseph M. Zmuda
  • Jane A. Cauley
  • Kristine E. Ensrud
  • Teresa A. Hillier
  • Marc C. Hochberg
  • Jia Li
  • Brian K. Rhees
  • Henry A. Erlich
  • Mark D. Sternlicht
  • Gary Peltz
  • Steven R. Cummings
  • For the Study of Osteoporotic Fractures (SOF) Research Group
Article

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 

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Gregory J. Tranah
    • 1
    • 2
  • Brent C. Taylor
    • 3
    • 4
  • Li-Yung Lui
    • 1
  • Joseph M. Zmuda
    • 5
  • Jane A. Cauley
    • 5
  • Kristine E. Ensrud
    • 3
    • 4
    • 6
  • Teresa A. Hillier
    • 7
  • Marc C. Hochberg
    • 8
  • Jia Li
    • 9
  • Brian K. Rhees
    • 9
  • Henry A. Erlich
    • 9
  • Mark D. Sternlicht
    • 10
  • Gary Peltz
    • 11
  • Steven R. Cummings
    • 1
    • 12
  • For the Study of Osteoporotic Fractures (SOF) Research Group
    • 13
  1. 1.CPMC Research InstituteSan FranciscoUSA
  2. 2.California Pacific Medical Center Research Institute, San Francisco Coordinating Center UCSFSan FranciscoUSA
  3. 3.Center for Chronic Disease Outcomes ResearchMinneapolis VA Medical CenterMinneapolisUSA
  4. 4.Division of Epidemiology and Community HealthUniversity of MinnesotaMinneapolisUSA
  5. 5.Department of EpidemiologyUniversity of PittsburghPittsburgUSA
  6. 6.Department of MedicineUniversity of MinnesotaMinneapolisUSA
  7. 7.Kaiser Permanente Center for Health Research Northwest/HawaiiPortlandUSA
  8. 8.Department of Medicine and Epidemiology and Preventative MedicineUniversity of Maryland School of Medicine UniversityBaltimoreUSA
  9. 9.Department of Human GeneticsRoche Molecular SystemsAlamedaUSA
  10. 10.Department of AnatomyUniversity of CaliforniaSan FranciscoUSA
  11. 11.Department of Genetics and GenomicsRoche Palo AltoPalo AltoUSA
  12. 12.Department of EpidemiologyUniversity of CaliforniaSan FranciscoUSA
  13. 13.San FranciscoUSA

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