Association between the methylenetetrahydrofolate reductase c.677C>T polymorphism and bone mineral density: an updated meta-analysis

Abstract

Many studies have reported an association between the methylenetetrahydrofolate reductase (MTHFR) c.677C>T polymorphism and reduced bone mineral density (BMD), but results have been inconsistent. We, therefore, performed a meta-analysis to further explore this association. Twenty-one studies, comprising 33,045 subjects, analyzed the association of MTHFR c.677C>T with femoral neck BMD. Significant association with reduced BMD was observed in Caucasians (recessive model: WMD = -0.004 g/cm(2), 95 % CI -0.008 to -0.006), post-menopausal women (recessive model: WMD = -0.005 g/cm(2), 95 % CI -0.007 to -0.003), men (dominant model: WMD = -0.004 g/cm(2), 95 % CI -0.005 to -0.004; recessive model: WMD = -0.004 g/cm(2), 95 % CI -0.005 to -0.004; TT vs. CC: WMD = -0.006 g/cm(2), 95 % CI -0.006 to -0.006; CT vs. CC: WMD = -0.003 g/cm(2), 95 % CI -0.003 to -0.003), and cohort studies (recessive model: WMD = -0.003 g/cm(2), 95 % CI -0.006 to -0.001). Twenty-two studies, which included 32,271 subjects, analyzed the MTHFR c.677C>T association with lumbar spine BMD. Significant association with reduced BMD was observed in Caucasians, women, post-menopausal women, men, and cohort studies. Seven studies, comprising 6806 subjects, analyzed the MTHFR c.677C>T association with total hip BMD, but no significant association was observed in any population. Nine studies involving 5591 subjects analyzed the association with total body BMD. Significant association with reduced BMD was observed in overall and women subgroup analyses. In summary, this meta-analysis indicates that the MTHFR c.677C>T polymorphism is associated with reduced BMD in lumbar spine and femoral neck in Caucasians, post-menopausal women, and men, and with total body BMD in women. In addition, our results suggest that new studies examining the association between MTHFR c.677C>T polymorphism and BMD of lumbar spine and femoral neck in Asians is warranted, because I (2) > 75.0 % was observed.

Homocysteine: Its Possible Emerging Role in At-Risk Population Groups

“…Moreover, oxidative damage and the adverse effects of Hcy on endothelial-derived nitric oxide could increase risk of fracture [182][183][184]. MTHFR polymorphism C667 T could also be involved in the increase of osteoporotic fracture incidence [181], and a recently published meta-analysis showed an association between MTHFR C667 T polymorphism and reduced bone mineral density in the lumbar spine and femoral neck in Caucasians, post-menopausal women, and men, and with total BMD in women [185]. Ahn et al [186] reported an association in 301 postmenopausal women between osteoporotic vertebral compression fractures and MTHFR and TS gene polymorphisms in the 3 -UTR region.…”

Haplotype-based genome-wide association studies for carcass and growth traits in chicken

“…MTHFR is methylenetetrahydrofolate reductase, which catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine. Variants within this gene have been associated with BMD ( Li et al., 2016 ). EPHB2 is EPH receptor B2.…”

Genetic variants of MTHFR gene in relation to folic acid levels and bone mineral density in Polish patients with inflammatory bowel disease

“…According to the meta-analysis, the MTHFR c.677C > T variant was linked to a decreased lumbar spine and femoral neck BMD in Caucasian men and postmenopausal women. This polymorphism was also associated with a reduced total body BMD in women (Li et al 2016 ). In fact, postmenopausal Thai women with the MTHFR 677 CT genotype presented a higher risk of osteopenia than the control group genotype (OR = 5.66; P -value < 0.001) (Tongboonchoo et al 2013 ).…”