Association of the MTHFR C677T polymorphism and bone mineral density in postmenopausal women: a meta-analysis

Abstract

Osteoporosis is a condition characterized by low bone mineral density (BMD) and micro-architectural changes in the bone tissue. The risk of osteoporosis is partly determined by genetic factors. The role of C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene has been investigated in postmenopausal osteoporosis. However, the relationship between MTHFR polymorphism and BMD is still controversial. We carried out a meta-analysis of 5,833 subjects to evaluate the association of MTHFR and BMD in postmenopausal women. Databases of MEDLINE, Web of Science, Scopus and CNKI were retrieved for all publications relating to MTHFR polymorphism and BMD in postmenopausal women. Five eligible studies were selected for meta-analysis. All these articles studied the association of MTHFR polymorphism and BMD of the femoral neck and lumbar spine in postmenopausal women. Our analysis suggested that postmenopausal women with the TT genotype had lower femoral neck BMD than the women with the CC/CT genotype, and the weighted mean difference (WMD) was -0.01 g/cm(2) [95% confidence interval (CI): (-0.01, -0.01), P < 0.01]. However, BMD of the lumbar spine of postmenopausal women with the TT genotype was not significantly different from that of women with the CC/CT genotype. In the random effects model, the WMD between the TT and TC/CC genotype was -0.01 g/cm(2) [95% CI: (-0.04, 0.01), P = 0.32]. The C677T polymorphism of the MTHFR gene is associated with BMD of the femoral neck in postmenopausal women. Women with the TT genotype of the MTHFR gene have lower BMD, suggesting that the TT genotype may be a risk factor for postmenopausal osteoporosis.

Keywords: bone mineral density; meta-analysis; methylenetetrahydrofolate reductase; postmenopausal women.

Fig. 1. Individual and pooled weighted mean difference estimates and their 95% confidence intervals (CI) for femoral neck and lumbar spine bone mineral density (BMD) in postmenopausal women.

The size of the square is proportional to the percent weight of each study in the fixed and random effect meta-analysis. Horizontal line represents the 95% CI. The summary pooled WMD and its 95%CI are indicated by the shaded diamond. A: femoral neck BMD in postmenopausal women. B: lumbar spine BMD in postmenopausal women.