RESUMO
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.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Proteína Morfogenética Óssea 15/genética , Receptor beta de Estrogênio/genética , Estrogênios/metabolismo , Fertilidade , Proteínas Nucleares/genética , Polimorfismo de Nucleotídeo Único , Transdução de Sinais , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adulto , Fatores Etários , Alelos , Proteína Morfogenética Óssea 15/metabolismo , Receptor beta de Estrogênio/metabolismo , Feminino , Frequência do Gene , Estudos de Associação Genética , Heterozigoto , Humanos , Menopausa , Proteínas Nucleares/metabolismo , Proteína 1 de Interação com Receptor Nuclear , Modelos de Riscos Proporcionais , EspanhaRESUMO
AIM: The purpose of this study is to confirm in our population the decreasing secular trend in the age of menarche (AAM) observed in other European countries. Another aim is to investigate the association between early menarche and breast cancer, metabolic disorders risk or early menopause. MATERIALS AND METHODS: We conducted a nationwide population-based study of 1980 Caucasoid Spanish postmenopausal women from 2003 to 2006 to investigate the AAM, the duration of the fertile period and the relation of early menarche with breast cancer and some metabolic disorders. RESULTS: Regression analysis of AAM demonstrates a trend towards the younger AAM in our population during the past decades (P > 0.001). Parallel to this decrease we observe a significant increase in the fertility period and the height of our population (P < 0.001). In the women with AAM less than 11 years, there is an increased risk of hypercholesterolaemia, being overweight and obesity. However, early menarche does not raise the risk of adult onset diabetes, hypertension or breast cancer. CONCLUSIONS: These data indicate a decreasing secular trend of AAM in a Spanish population in the last decades. Furthermore, hypercholesterolaemia and obesity, but not breast cancer, appears to be influenced by younger AAM. Only women who have their menarche at the age of nine years or less are more likely to have an earlier menopause.