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. Material and 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.

Keywords::

• Fertile period
• estrogen-related genes
• polymorphism

Acknowledgements

We acknowledge Francisco Quereda (Hospital Universitario San Juan, Alicante); Txantón Martínez Astorquiza (Hospital Cruces, Bilbao) and Francisco Vázquez (Clínica GEOGA, Lugo) for the recruitment of the patients.

Declaration of Interest: The authors declare no conflicts of interest.