Objective: To assess the interrelation of the MTHFR ala222val polymorphism, correlated with increased rates of cardiovascular disease, with indices of androgenicity in healthy postmenopausal women.
Methods: The population of this cross-sectional study consisted of 84 healthy women who had been menopausal for at least one year. The examined polymorphism was Methylenetetrahydrofolate reductase ala222val, while the hormonal assays included Testosterone, Sex Hormone Binding Globulin (SHBG), Dehydroepiandrosterone sulphate (DHEAS), Δ-4-androstendione (Δ4A), free androgen index (FAI) and the aminoacid homocysteine (Hcy). Written informed consent was obtained by all participants. The local Institutional Review Board has approved the present study.
Results: MTHFR ala222val polymorphism was positively associated with serum testosterone, DHEAS, Δ4A and FAI (P=0.001, P=0.053, P=0.054, P=0.0004 respectively) and negatively with SHBG (P=0.047). No significant association was found between MTHFR ala222val polymorphism and homocysteine levels.
Conclusions: The presence of MTHFR ala222val polymorphism was associated with indices of androgenicity in healthy postmenopausal women, but it was not associated with hyperhomocysteinemia at a statistically significant level. Insulin resistance, which has been correlated with increased androgenicity, may act as a mediator. MTHFR ala222val polymorphism and the following impaired homocysteine catabolism induce, at a cellular level, endothelial dysfunction along with insulin resistance. This metabolic manifestation associates with increased androgenicity.