Bone density and body weight is associated with MTHFR677 polymorphism in girls with anorexia nervosa

Abstract

Introduction: Anorexia nervosa (AN) is associated with dysfunction of the hypothalamus-pituitary-gonadal axis, and thus with adverse effects on skeletal integrity. We aimed to identify the combination of polymorphisms linked to deterioration of bone health in a sample of adolescent girls with AN.
Patients and Methods: The sample of this cross-sectional study consisted of 40 young girls (12-21 years old), diagnosed with AN according to the American Psychiatry Association criteria. A detailed medical history was recorded for each participant and blood samples were taken for hormonal evaluation and genotyping. Lumbar spine bone density (bone mineral density, BMD) was evaluated using dual energy X-ray absorptiometry.
Results: Lower BMD values were observed in girls with: i) presence of the CTR-AluI polymorphism vs wild type (BMD, CC&CT vs TT genotypes: 0.84±0.21g/cm2 vs 0.96±0.12g/cm2, p-value=0.028); ii) presence of the MTHFR677T polymorphism vs wild type (BMD, TT&CT vs CC genotypes: 0.86±0.23g/cm2 vs 0.94±0.11g/cm2, p-value=0.047, adjusted for age, BMI, amenorrhoea). BMD measures exhibited a graded stepwise decrease with the addition of the CTR-AluI and/or the MTHFR677 polymorphic variant (BMD, wild type vs one vs two polymorphic variants: 0.97±0.11g/cm2 vs 0.90±0.11g/ cm2 vs 0.75±0.33g/cm2, p-value for linear trend 0.011). Girls carrying the MTHFR677 polymorphism had 5.67-times higher odds of having a higher BMI (BMI >16.4kg/m2 vs ≤16.4kg/m2, MTHFR677 polymorphism, CT&TT vs CC genotypes: OR=5.667, 95% CI: 1.254—25.606, p-value=0.024).
Conclusion: Combined presence of the MTHFR677 and CTR-AluI polymorphisms is associated with lower bone density in young girls with AN, implying a dose-response effect. The association between MTHFR677 and bone metabolism is likely mediated by body weight.

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