ArticleOsteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA2005
Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is associated with osteoporotic vertebral fractures, but is a weak predictor of BMD.
Article in Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 3 of them syntheses that pooled it.
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27 citing papers in PubMed, 3 syntheses or guidelines pooled it, 72 citations in OpenAlex.
- Association between the methylenetetrahydrofolate reductase c.677C>T polymorphism and bone mineral density: an updated meta-analysis.Molecular genetics and genomics : MGG · 2016Pooled it
- Quantitative assessment of the associations between MTHFR C677T and A1298C polymorphisms and risk of fractures: a meta-analysis.Molecular biology reports · 2013Pooled it
- Association of MTHFR C667T polymorphism with bone mineral density and fracture risk: an updated meta-analysis.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2012Pooled it
- Expanding the Phenotypic Spectrum of Methylenetetrahydrofolate Reductase (MTHFR) Deficiency in Childhood: A Case Series.Clinical case reports · 2025Article
- Article
- Does Folic Acid Protect Patients with Inflammatory Bowel Disease from Complications?Nutrients · 2021Review
- The Effects of Homocysteine on the Skeleton.Current osteoporosis reports · 2018Review
- Association of Bone Turnover Levels with MTHFR Gene Polymorphisms among Pregnant Women in Wuhan, China.Current medical science · 2018Article
- A comprehensive overview on osteoporosis and its risk factors.Therapeutics and clinical risk management · 2018Review
- Association of Plasminogen Activator Inhibitor-1 (PAI-1) Gene Polymorphisms with Osteoporotic Vertebral Compression Fractures (OVCFs) in Postmenopausal Women.International journal of molecular sciences · 2016Article
- Association of Methylene Tetrahydrofolate Reductase Polymorphism with BMD and Homocysteine in Premenopausal North Indian Women.Journal of clinical and diagnostic research : JCDR · 2013Article
- Association of the MTHFR C677T polymorphism and bone mineral density in postmenopausal women: a meta-analysis.Journal of biomedical research · 2010Article
- Genome-wide pleiotropy of osteoporosis-related phenotypes: the Framingham Study.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2010Article
- Review
- The genetics of response to estrogen treatment.Clinical cases in mineral and bone metabolism : the official journal of the Italian Society of Osteoporosis, Mineral Metabolism, and Skeletal Diseases · 2009Article
- Associations between methotrexate treatment and methylenetetrahydrofolate reductase gene polymorphisms with incident fractures in Japanese female rheumatoid arthritis patients.Journal of bone and mineral metabolism · 2009Article
- Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is associated with spinal BMD in 9-year-old children.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2009Article
- Strontium ranelate decreases plasma homocysteine levels in postmenopausal osteoporotic women.Rheumatology international · 2009Article
- Genetic variation in candidate osteoporosis genes, bone mineral density, and fracture risk: the study of osteoporotic fractures.Calcified tissue international · 2008Article
- Genetics of the musculoskeletal system: a pleiotropic approach.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2008Article
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5 authors.
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Abstract
Osteoporosis is a common disease with a strong genetic component. Linkage studies have suggested linkage between BMD and loci on chromosome 1. The MTHFR gene is located on chromosome 1. MTHFR catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methylenetetrahydrofolate, which is used for homocysteine methylation to methionine. The rare genotype (TT) of the C677T polymorphism has previously been demonstrated to be associated with increased plasma homocysteine levels in individuals with inadequate plasma folate levels. Recently, the TT genotype has been found to be associated with reduced bone mass. We therefore examined if the C677T polymorphism in the MTHFR gene is associated with changes in bone mass and risk of osteoporotic fractures in 388 osteoporotic patients and 336 normal individuals. The distributions of the genotypes CC, CT and TT in women with osteoporotic vertebral fractures and normal controls were 43.5%, 42.2% and 14.3% and 52.0%, 42.0% and 8.0%, respectively, chi2 = 5.62, P = 0.06. Since studies of the functionality of this polymorphism have revealed that only the TT genotype is associated with biochemical changes, we also compared the prevalence of the TT genotype versus the CT- and CC genotypes in patients and controls and found that the TT genotype is significantly more common in women with vertebral fractures (14.3%) compared with normal controls (8.0%), chi2 = 4.31, P < 0.05. Logistic regression analysis demonstrated that vertebral fractures were significantly associated with BMD (lumbar spine) and height but only marginally with the MTHFR genotype (P = 0.06). Multiple linear regression analysis revealed that weight, age and the MTHFR polymorphism were predictors of lumbar spine BMD in women. However, age- and gender-corrected BMD of the lumbar spine and the hip was not significantly different between MTHFR genotypes. Furthermore, individuals with the TT genotype did not have BMD significantly lower than the combined group of individuals with the CT- or CC genotypes. In conclusion, we have demonstrated that the rare TT genotype of the C677T polymorphism in the MTHFR gene is associated with increased risk of osteoporotic fractures in women and a weak predictor of lumbar spine BMD.
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