Polymorphisms of
methylenetetrahydrofolate reductase (MTHFR) have been well documented to cause
hyperhomocysteinemia, and recent studies suggest an association of C677T mutation of
methylenetetrahydrofolate reductase with
low bone mineral density (BMD). In this study, the association of plasma total
homocysteine (Hcy), plasma
folate, and
vitamin B12 as well as
methylenetetrahydrofolate reductase C667T polymorphism with bone mineral density at neck of femur and lumbar spine in 271 postmenopausal Iranian women was investigated. Bone mineral density was measured by dual-energy X-ray absorptiometry. Restriction fragment length polymorphism was used for genotyping the
methylenetetrahydrofolate reductase polymorphism. Plasma total
homocysteine, plasma
folate, and
vitamin B12 were also determined. The bone mineral densities at the neck of femur and lumbar spine together with other clinical characteristics among
methylenetetrahydrofolate reductase genotypes (CC, CT, and TT) were examined. Bone mineral densities at both neck of femur (r = -0.18, P = 0.003) and lumbar spine (r = -0.16, P = 0.01) were significantly and negatively correlated with the logarithm of plasma total
homocysteine. Bone mineral density at the lumbar spine was also significantly and positively associated with plasma
folate (r = 0.14, P = 0.02). However, no correlation between
methylenetetrahydrofolate reductase polymorphism with bone mineral density at neck of femur (r = -0.01, P = 0.81) and lumbar spine (r = -0.04, P = 0.51) was observed. The negative association of plasma total
homocysteine with bone mineral density was no longer significant when adjusted for
folate and
vitamin B12. Plasma
folate and age were the main predictors of plasma total
homocysteine explaining 15.3% and 5.2% of the variance of plasma total
homocysteine, respectively.
Methylenetetrahydrofolate reductase polymorphism, however, was not associated with plasma
folate (r = 0.086, P = 0.17) or
vitamin B12 (r = 0.05, P = 0.4). Plasma
folate was one of the main predictors explaining 3.0% and 1.7% of variance of the bone mineral density at femoral neck and lumbar spine, respectively. Results from this study suggest
hyperhomocysteinemia as a result of
folate deficiency, but not
methylenetetrahydrofolate reductase polymorphism, is independently associated with
low bone mineral density and may contribute to the pathogenicity of
osteoporosis in postmenopausal Iranian women.