No association of estrogen receptor α and cytochrome P450c17α polymorphisms with age at menopause in a Dutch cohort

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Abstract
BACKGROUND: Age at menopause is under strong genetic control. So far, genetic variations of only one gene, the PvuII polymorphism of the estrogen receptor α (ERα) gene, have been shown to be associated with age at onset of menopause. This study aims to investigate whether PvuII, XbaI and B-variant polymorphisms of the ERα gene, and the MspAI polymorphism of the cytochrome P450c17α (CYP17) gene are associated with age at menopause in a Dutch cohort. METHODS: DNA was isolated from urine samples of 385 Caucasian women with natural menopause and the genotypes of the four polymorphisms were determined. A questionnaire was used for background characteristics. The genotypes of PvuII, XbaI, MspAI were obtained by PCR restriction fragment length polymorphism analysis. The B-variant was determined with an allele-specific oligonucleotide hybridization method. Two-sided t-tests were performed to assess the association between the four polymorphisms and menopausal age. The PvuII and XbaI polymorphisms were analysed separately as well as in a combined score. RESULTS: The results show that none of the polymorphisms independently, nor the combined genotypes for PvuII and XbaI, were associated with age at natural menopause. CONCLUSION: No evidence was found for a relationship between common variants of the ERα gene and the CYP17 gene with age at natural menopause.