Abstract for presentation at 11th International Congress of Human Genetics

A cohort study of the effects of MTHFR genotypes on bone structure 1214 elderly women

  • Ms Melinda Soόs, University of Western Australia, Australia
  • Dr Amanda Devine, Edith Cowan University, Australia
  • Dr Ian Dick, The Western Australian Centre for Pathology and Medical Research, Australia
  • Dr John Beilby, University of Western Australia, Australia
  • Dr Richard Prince, University of Western Australia, Australia

    • Osteoporosis (OP) is a disease of profound epidemiological and economic importance. The phenotype which best defines OP is a low bone mineral density (BMD) measured at the hip using dual energy X-ray absorptiometry (DXA). We (Wilson SG et al. Am J Hum Genet 2003;72:144-55) and others have shown linkage between low BMD and the 1p36 region which contains the methyeneltetrahydrofolate reductase (MTHFR) gene. Others have reported associations between these genotypes and bone phenotypes. We have reported that two mutations in the MTHFR gene sequence C677T and A1298C result in altered MTHFR activity and thereby influence folate and homocysteine levels in conjunction with dietary folate intake. In this study we examine the effects of the resulting homocysteine levels and the MTHFR genotypes, determined by Hinfl and MboII digestion, on DXA hip BMD at baseline and 4 years later and fracture rates over 4 years determined from x-ray reports.
    The highest tertile of homocysteine was associated with a significantly greater hip DXA BMD loss over 4 years compared to the middle and bottom tertiles (top 22±3 mg/cm2; middle middle 12±3 mg/cm2; bottom 10±3 mg/cm2 P < 0.05) but not the baseline or 4 year DXA BMD or incident fracture. There was no relationship between the MTHFR genotypes and baseline, 4 year or change in hip BMD or incident fracture susceptibility.
    Homocysteine levels are in part regulated by MTHFR genotypes and high levels are associated with bone loss. However, the genotype effect alone is not large enough to affect bone phenotypes.

    Conference Organiser - ICMS Pty Ltd