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The synergistic effect of bone mineral density and methylenetetrahydrofolate reductase (MTHFR) polymorphism (C677T) on fractures

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Abstract

A functional polymorphism in methylenetetrahydrofolate reductase (MTHFR) has been identified at codon 677 (C677T). The T-allele variant (valine type) has lower enzyme activity than the wild type (C-allele or alanine type), resulting in a slightly elevated homocysteine level, which has been recently recognized as a risk factor for fracture. However, whether subjects bearing the T allele have higher susceptibility to fractures is still controversial. We have investigated the effects of MTHFR polymorphism on fracture susceptibility in Japanese postmenopausal women. A total of 502 postmenopausal ambulatory Japanese women were followed up for 5.1 ± 3.4 (mean ± SD) years, and a total of 155 patients with incident fractures (121 patients with vertebral fractures and 34 cases with fractures at other sites) were recorded. When compared with the patients without any fractures, the patients with incident fractures were older, had more prevalent fractures, had higher urinary levels of bone turnover markers as well as plasma homocysteine level, but were shorter in body height and had lower bone mineral density. The prevalence of the TT genotype of MTHFR was significantly higher in the patients with incident fractures compared to the other genotypes. The subjects with the TT genotype had a higher incidence rate of fracture and higher plasma level of homocysteine than the subjects bearing the non-TT genotype. This relationship was observed in both osteoporotic and nonosteoporotic groups. The hazard ratio for TT genotype without osteoporosis, non-TT genotype with osteoporosis, and TT genotype with osteoporosis was 1.49 (0.91–2.45), 3.64 (2.50–5.29), and 7.21 (4.34–11.97), respectively, compared to the non-TT genotype without osteoporosis. A higher hazard ratio for the TT genotype with osteoporosis was still apparent after adjustment for age, body size, and number of prevalent vertebral fractures. These results indicate that the TT genotype of MTHFR may be a risk factor for future fracture in addition to the traditional risk factors.

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Authors and Affiliations

  1. Department of Internal Medicine, Research Institute and Practice for Involutional Diseases, 1610-1 Meisei, Misato, Azumino, Nagano, 399-8101, Japan

    Masataka Shiraki

  2. Department of Coca-Cola Anti-Aging Medicine, Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Tomohiko Urano & Satoshi Inoue

  3. Department of Obstetrics and Gynecology, Tokyo Women’s Medical University, Tokyo, Japan

    Tatsuhiko Kuroda

  4. Department of Orthopedic Surgery, Jikei University School of Medicine, Tokyo, Japan

    Mitsuru Saito

  5. Department of Epidemiology and Biostatistics, Tokyo University, Tokyo, Japan

    Shiro Tanaka

  6. Department of Endocrinology and Metabolism, Kantou Central Hospital, Tokyo, Japan

    Mariko Miyao-Koshizuka

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  1. Masataka Shiraki
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  4. Mitsuru Saito
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Correspondence to Masataka Shiraki.

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Shiraki, M., Urano, T., Kuroda, T. et al. The synergistic effect of bone mineral density and methylenetetrahydrofolate reductase (MTHFR) polymorphism (C677T) on fractures. J Bone Miner Metab 26, 595–602 (2008). https://doi.org/10.1007/s00774-008-0878-9

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  • DOI: https://doi.org/10.1007/s00774-008-0878-9

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