Age at menarche and menopause is not associated with two common genetic variants in the methylenetetrahydrofolate reductase (MTHFR) gene

OBJECTIVES: The study aimed at investigating the independent and the combined effects of the two common genetic variants in the methylenetetrahydrofolate reductase (MTHFR) gene, 677C > T and 1298A > C, and their interaction with lifestyle factors on timing of menarche and natural menopause. METHODS: Postmenopausal women (N = 792) were assessed for the association of the two genetic variants with age at menarche (AM). A subsample of 578 of them who had a natural menopause were further investigated for the association of the two genetic variants with age at natural menopause (ANM). Genotyping was done by means of the TaqMan(®) allelic discrimination method. The effect of genetic variants and of lifestyle factors on AM and ANM were calculated by linear regression models. RESULTS: The study revealed no association between the individual or combined effects of the two genetic variants and AM or ANM. The genetic variant 677C > T showed a significant interaction effect with duration of breastfeeding on ANM (p = 0.047). CONCLUSION: We were unable to replicate previous findings suggesting that the MTHFR gene influences the onset of menarche and natural menopause. The interaction effect between the 677C >T genetic variant and duration of breastfeeding on the timing of natural menopause requires further investigation.