title: Age at menarche and menopause is not associated with two common genetic variants in the methylenetetrahydrofolate reductase (MTHFR) gene.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Medical Genetics, Department of Obstetrics and Gynaecology, University Medical Centre Ljubljana, Slovenia.
authors.forename: Jasmina-Ziva
authors.initials: JZ
authors.lastname: Cerne
authors.forename: Maja
authors.initials: M
authors.lastname: Pohar-Perme
authors.forename: Petra
authors.initials: P
authors.lastname: Cerkovnik
authors.forename: Ksenija
authors.initials: K
authors.lastname: Gersak
authors.forename: Srdjan
authors.initials: S
authors.lastname: Novakovic
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000368:Aged; D001942:Breast Feeding; D002648:Child; D005260:Female; D005838:Genotype; D006801:Humans; D008019:Life Style; D016014:Linear Models; D008572:Menarche / Q000235:genetics*; D008593:Menopause / Q000235:genetics*; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012907:Smoking
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2)