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

ABSTRACT

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.

KEYWORDS:

• Age at menarche
• Age at menopause
• Methylenetetrahydrofolate reductase
• Genetic variant
• Association study

ACKNOWLEDGEMENT

This work was supported by grant L3-0431 from the Slovenian Research Agency.

We would like to thank Ms Mojca Pirc for revision of the English text.

Declaration of interest: The authors report no conflict of interest. The authors alone are responsible for the content and the writing of the paper.