No association of estrogen receptor alpha and cytochrome P450c17alpha polymorphisms with age at menopause in a Dutch cohort.
BACKGROUND
Age at menopause is under strong genetic control. So far, genetic variations of only one gene, the PvuII polymorphism of the estrogen receptor alpha (ERalpha) 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 ERalpha gene, and the MspAI polymorphism of the cytochrome P450c17alpha (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.


CONCLUSIONS
No evidence was found for a relationship between common variants of the ERalpha gene and the CYP17 gene with age at natural menopause.
Kok
Helen S
HS
Julius Center for Health Sciences and Primary Care, Department of Medical Genetics, University Medical Center Utrecht, The Netherlands.
Onland-Moret
N Charlotte
NC
van Asselt
Kristel M
KM
van Gils
Carla H
CH
van der Schouw
Yvonne T
YT
Grobbee
Diederick E
DE
Peeters
Petra H M
PH
D000367:Age Factors; D015331:Cohort Studies; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D006801:Humans; D008593:Menopause / Q000235:genetics*; D008875:Middle Aged; D009426:Netherlands; D011110:Polymorphism, Genetic; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics*
D047628:Estrogen Receptor alpha; D013254:Steroid 17-alpha-Hydroxylase