Endocrine Abstracts

Objectives: To study the association of functional polymorphisms at DHFR, CBS and MTHFR genes with bone mineral density (BMD) and metabolic parameters of bone remodeling.

Materials and methods: BMD (g/cm2) was measured by DEXA in 391 subjects: 174 with normal BMD (137F 37M; age=48.79±12.99 years; BMI=29.61±5.22 kg/m2), 62 with osteopenia (48F 14M; age=56.06±12.96 years; BMI=27.64±4.94 kg/m2) and 154 with osteoporosis (119F, 35M; age=64.17±11.04 years; BMI=27.48±4.56 kg/m2). Metabolic bone remodeling parameters were analyzed: LDL, HDL, total cholesterol, triglycerides, HOMA, parathormone (PTH), alkaline phosphatase (AP), bone fraction of alkaline phosphatase (AP_BF) and osteocalcin. Genetic polymorphisms were evaluated by PCR and PCR-RFLP. Statistical analysis by SPSS 23.0. Statistical significance for P<0.05.

Results: The three studied groups differ in age and BMI being those with osteoporosis the oldest and with the lower BMI. Individuals with reduced BMD (osteopenia and osteoporosis) showed higher PTH and osteocalcin. Those with osteoporosis also showed higher AP. Individuals with allele C of MTHFR_C677T polymorphism (CC or CT) showed a 2.194 risk for the development of reduced BMD (P=0.024; OR=2.194; CI95% [1.109–4.342]) when adjusted for age and BMI. For the studied polymorphisms at DHFR and CBS genes we did not find association with the susceptibility for osteopenia or osteoporosis. When we compared metabolic bone remodeling parameters within genotypes of the studied polymorphisms, we found: For DHFR we did not find statistical differences when we included the all studied population. Although, we found lower AP, AP_BF and total cholesterol for DHFR_ins/ins genotype in normal BMD individuals. For CBS we did not find statistical differences when we included the all studied population. Although, we found lower AP and AP_BF for CBS_-/- genotype in osteoporotic individuals. For MTHFR we found higher AP and AP_BF and lower HDL for CC individuals, and higher osteocalcin for Individuals with allele C (CC or CT) when we included the all studied population. When we separated individuals according to their BMD, we found lower HDL and total cholesterol and higher osteocalcin for osteoporotic individuals carrying allele C (CC or CT).

Conclusion: MTHFR_C677T polymorphism seems to confer susceptibility for reduced bone mass, either directly or by modulating metabolic bone remodeling parameters. On the other hand, genetic polymorphisms of DHFR and CBS seem to play and important role in modulating metabolic bone remodeling parameters associated with reduced bone mineral density.