title: A multigenic combination of estrogen related genes are associated with the duration of fertility period in the Spanish population.
abstract: OBJECTIVE
  The duration of the fertile period (FP) can be considered a complex parameter that depends on the interaction of multiple factors. In the present study, the role of interaction between genetic variants within estrogen synthesis and signaling pathways in the FP in Spanish women is studied.
  
  
  METHODS
  Nine single nucleotide polymorphisms (SNPs) located at different candidate genes related to the estrogen signaling pathway were analyzed in 1980 Spanish postmenopausal women.
  
  
  RESULTS
  Independently, none of the nine markers were significantly associated with age at menopause. In contrast, survival analysis techniques suggest several epistatic interactions including these markers in relation to age at menopause, especially between ESR2, NRIP1 and BMP15: women who showed the three markers ESR2 (AA), BMP15 (rs3897937) (TC) and NRIP1 (AA), the FP was shorter than the control group of women without any of these markers (32.36 ± 1.49 versus 34.94 ± 0.32 years; p = 0.026). The digenic BMP15 (rs3897937) (TC) and NRIP1 (AA) combination were also associated with a decreased duration of the FP (33.32 ± 0.96 years, p = 0.031).
  
  
  CONCLUSIONS
  The results suggest that interactions of estrogen-related alleles may contribute to variance in FP in Spanish women.
authors.affiliation: Department of Obstetrics and Gynecology, University of Granada, Granada,Spain. nicomendoza@telefonica.net
authors.forename: Nicolás
authors.initials: N
authors.lastname: Mendoza
authors.forename: Juan Eloy Ruiz
authors.initials: JE
authors.lastname: Castro
authors.forename: Rafael
authors.initials: R
authors.lastname: Sánchez Borrego
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000367:Age Factors; D000483:Alleles; D055430:Bone Morphogenetic Protein 15 / Q000235:genetics* / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics* / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D005298:Fertility; D005787:Gene Frequency; D056726:Genetic Association Studies; D006579:Heterozygote; D006801:Humans; D008593:Menopause; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D000078723:Nuclear Receptor Interacting Protein 1; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D015398:Signal Transduction; D013030:Spain
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C525901:BMP15 protein, human; D055430:Bone Morphogenetic Protein 15; D047629:Estrogen Receptor beta; D004967:Estrogens; D009687:Nuclear Proteins; D000078723:Nuclear Receptor Interacting Protein 1