Article

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

  • Gregory J. TranahAffiliated withCPMC Research InstituteCalifornia Pacific Medical Center Research Institute, San Francisco Coordinating Center UCSF Email author 
  • , Brent C. TaylorAffiliated withCenter for Chronic Disease Outcomes Research, Minneapolis VA Medical CenterDivision of Epidemiology and Community Health, University of Minnesota
  • , Li-Yung LuiAffiliated withCPMC Research Institute
  • , Joseph M. ZmudaAffiliated withDepartment of Epidemiology, University of Pittsburgh
  • , Jane A. CauleyAffiliated withDepartment of Epidemiology, University of Pittsburgh
  • , Kristine E. EnsrudAffiliated withCenter for Chronic Disease Outcomes Research, Minneapolis VA Medical CenterDivision of Epidemiology and Community Health, University of MinnesotaDepartment of Medicine, University of Minnesota
  • , Teresa A. HillierAffiliated withKaiser Permanente Center for Health Research Northwest/Hawaii
  • , Marc C. HochbergAffiliated withDepartment of Medicine and Epidemiology and Preventative Medicine, University of Maryland School of Medicine University
  • , Jia LiAffiliated withDepartment of Human Genetics, Roche Molecular Systems
    • , Brian K. RheesAffiliated withDepartment of Human Genetics, Roche Molecular Systems
    • , Henry A. ErlichAffiliated withDepartment of Human Genetics, Roche Molecular Systems
    • , Mark D. SternlichtAffiliated withCPMC Research InstituteDepartment of Anatomy, University of California
    • , Gary PeltzAffiliated withCPMC Research InstituteDepartment of Genetics and Genomics, Roche Palo Alto
    • , Steven R. CummingsAffiliated withCPMC Research InstituteDepartment of Epidemiology, University of California
    • , For the Study of Osteoporotic Fractures (SOF) Research GroupAffiliated withCPMC Research Institute

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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.

Keywords

Genetics Polymorphism Osteoporosis BMD Fracture