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Evidence for an association of methylene tetrahydrofolate reductase polymorphism C677T and an increased risk of fractures: results from a population-based Danish twin study

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Abstract

Osteoporotic fractures are some of the major causes of morbidity and health care expenditure among the elderly. Identifying subjects at risk could be of major importance since several preventive treatments are now available. A large genetic component in the development of osteoporosis has been established. Previous studies concerning association of the common point mutation C677T in methylentetrahydrofolate reductase (MTHFR) and osteoporosis have revealed contradictory results. The aim of this study was to test the association between the MTHFR polymorphism, homocysteine, and fractures in a population-based sample of Danish twins aged 73+. In total, 689 subjects, with a mean age of 78 years, participated. Genotype and data of fractures are available from 687 subjects—144 with a previously diagnosed fracture. The genotype distribution is as follows: CC, CT, and TT genotypes, 317 (46.1%), 298 (43.3%), and 73 (10.6%), respectively. Using the proportional odds-ratio model adjusted for age, gender, and body mass Index, the odds-ratio of fracture was 1.5 per number of T alleles—meaning that fracture risk is 1.5 times higher in the CT group compared with the CC group and again 1.5 times higher in the TT group compared with the CT group. Homocysteine, smoking, and self-reported hormone use provided no significant contribution to fracture risk. Using biometrical modelling, the heritability of the liability to fractures was found to be approximately 0.10, when the effect of the MTHFR locus was included, and 0.07 when it was omitted. But both confidence intervals include zero and the estimates are therefore not significant. In conclusion, we here provide evidence for a significant impact of the MTHFR genotype on the occurrence of fractures in an elderly Danish population.

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Acknowledgement

This work was supported by the U.S. National Institute on Aging research grant NIA-P01-AG08761 and Johan Boserup and Lise Boserup’s Foundation.

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Authors and Affiliations

  1. Department of Clinical Biochemistry, Odense University Hospital, 5000, Odense, Denmark

    Lise Bathum, Lene Christiansen & Jonna Skov Madsen

  2. Department of Epidemiology, Institute of Public Health, and the Danish Centre for Demographic Research, University of Southern Denmark, 5000, Odense, Denmark

    Lise Bathum, Jacob von Bornemann Hjelmborg, Axel Skytthe & Kaare Christensen

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  1. Lise Bathum
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  2. Jacob von Bornemann Hjelmborg
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  3. Lene Christiansen
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  4. Jonna Skov Madsen
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  5. Axel Skytthe
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  6. Kaare Christensen
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Correspondence to Lise Bathum.

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Bathum, L., von Bornemann Hjelmborg, J., Christiansen, L. et al. Evidence for an association of methylene tetrahydrofolate reductase polymorphism C677T and an increased risk of fractures: results from a population-based Danish twin study. Osteoporos Int 15, 659–664 (2004). https://doi.org/10.1007/s00198-003-1584-z

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  • DOI: https://doi.org/10.1007/s00198-003-1584-z

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