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A common methylenetetrahydrofolate reductase (C677T) polymorphism is associated with low bone mineral density and increased fracture incidence after menopause: longitudinal data from the Danish osteoporosis prevention study.

Abstract

A polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR) has recently been associated with bone mineral density (BMD) in postmenopausal Japanese women. It is not known whether this effect is also present in European populations and whether it is caused by lower peak bone mass or accelerated postmenopausal bone loss. MTHFR genotyping was done in 1748 healthy postmenopausal Danish women participating in a prospective study of risk factors for osteoporosis. At the time of enrollment, 3-24 months after last menstrual period, the less prevalent genotype (TT, 8.7% of the population) was associated with significantly lower BMD at the femoral neck (ANOVA, p < 0.05), total hip (p < 0.01), and spine (p < 0.05 adjusted for lifestyle covariates, p = 0.06 without adjustment). The mean difference was between 0.1 and 0.3 SD, depending on measurement site. MTHFR genotype added significantly to prediction of BMD by weight and age. Fracture incidence was increased more than 2-fold in subjects with the TT genotype (risk ratio [RR], 2.6; 95% CI 1.2-5.6). This remained significant when the Cox analysis was controlled for BMD (RR, 2.4; 95% CI 1.1-5.2). No differences in serum osteocalcin, bone-specific alkaline phosphatase, and 25-OH-vitamin D were found between genotypes. The response to hormone replacement therapy (HRT) did not differ, but the association of the TT genotype with reduced BMD was maintained at the total hip after 5 years of HRT. The MTHFR TT genotype is associated with low BMD and increased fracture incidence in early postmenopausal women.

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  • Authors+Show Affiliations

    ,

    Department of Endocrinology, Odense University Hospital, Odense, Denmark. B.abrahamsen@dadlnet.dk

    , , , , , ,

    Source

    MeSH

    Alleles
    Bone Density
    Denmark
    Estrogen Replacement Therapy
    Female
    Fractures, Bone
    Gene Frequency
    Genotype
    Humans
    Longitudinal Studies
    Methylenetetrahydrofolate Reductase (NADPH2)
    Middle Aged
    Osteoporosis, Postmenopausal
    Polymorphism, Genetic
    Proportional Hazards Models
    Prospective Studies
    Risk Factors

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    12674333

    Citation

    Abrahamsen, Bo, et al. "A Common Methylenetetrahydrofolate Reductase (C677T) Polymorphism Is Associated With Low Bone Mineral Density and Increased Fracture Incidence After Menopause: Longitudinal Data From the Danish Osteoporosis Prevention Study." Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, vol. 18, no. 4, 2003, pp. 723-9.
    Abrahamsen B, Madsen JS, Tofteng CL, et al. A common methylenetetrahydrofolate reductase (C677T) polymorphism is associated with low bone mineral density and increased fracture incidence after menopause: longitudinal data from the Danish osteoporosis prevention study. J Bone Miner Res. 2003;18(4):723-9.
    Abrahamsen, B., Madsen, J. S., Tofteng, C. L., Stilgren, L., Bladbjerg, E. M., Kristensen, S. R., ... Mosekilde, L. (2003). A common methylenetetrahydrofolate reductase (C677T) polymorphism is associated with low bone mineral density and increased fracture incidence after menopause: longitudinal data from the Danish osteoporosis prevention study. Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, 18(4), pp. 723-9.
    Abrahamsen B, et al. A Common Methylenetetrahydrofolate Reductase (C677T) Polymorphism Is Associated With Low Bone Mineral Density and Increased Fracture Incidence After Menopause: Longitudinal Data From the Danish Osteoporosis Prevention Study. J Bone Miner Res. 2003;18(4):723-9. PubMed PMID: 12674333.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - A common methylenetetrahydrofolate reductase (C677T) polymorphism is associated with low bone mineral density and increased fracture incidence after menopause: longitudinal data from the Danish osteoporosis prevention study. AU - Abrahamsen,Bo, AU - Madsen,Jonna Skov, AU - Tofteng,Charlotte Landbo, AU - Stilgren,Lis, AU - Bladbjerg,Else Marie, AU - Kristensen,Søren Risom, AU - Brixen,Kim, AU - Mosekilde,Leif, PY - 2003/4/4/pubmed PY - 2003/12/5/medline PY - 2003/4/4/entrez SP - 723 EP - 9 JF - Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research JO - J. Bone Miner. Res. VL - 18 IS - 4 N2 - A polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR) has recently been associated with bone mineral density (BMD) in postmenopausal Japanese women. It is not known whether this effect is also present in European populations and whether it is caused by lower peak bone mass or accelerated postmenopausal bone loss. MTHFR genotyping was done in 1748 healthy postmenopausal Danish women participating in a prospective study of risk factors for osteoporosis. At the time of enrollment, 3-24 months after last menstrual period, the less prevalent genotype (TT, 8.7% of the population) was associated with significantly lower BMD at the femoral neck (ANOVA, p < 0.05), total hip (p < 0.01), and spine (p < 0.05 adjusted for lifestyle covariates, p = 0.06 without adjustment). The mean difference was between 0.1 and 0.3 SD, depending on measurement site. MTHFR genotype added significantly to prediction of BMD by weight and age. Fracture incidence was increased more than 2-fold in subjects with the TT genotype (risk ratio [RR], 2.6; 95% CI 1.2-5.6). This remained significant when the Cox analysis was controlled for BMD (RR, 2.4; 95% CI 1.1-5.2). No differences in serum osteocalcin, bone-specific alkaline phosphatase, and 25-OH-vitamin D were found between genotypes. The response to hormone replacement therapy (HRT) did not differ, but the association of the TT genotype with reduced BMD was maintained at the total hip after 5 years of HRT. The MTHFR TT genotype is associated with low BMD and increased fracture incidence in early postmenopausal women. SN - 0884-0431 UR - https://www.unboundmedicine.com/medline/citation/12674333/A_common_methylenetetrahydrofolate_reductase__C677T__polymorphism_is_associated_with_low_bone_mineral_density_and_increased_fracture_incidence_after_menopause:_longitudinal_data_from_the_Danish_osteoporosis_prevention_study_ L2 - https://doi.org/10.1359/jbmr.2003.18.4.723 DB - PRIME DP - Unbound Medicine ER -