The association between vascular function-related genes and age at natural menopause.
OBJECTIVE
In this study we attempted to confirm recent findings suggesting that age at natural menopause might be affected by single nucleotide polymorphisms in certain cardiovascular risk factor genes, such as genes encoding for blood clotting factors II, V, and VII and the apolipoprotein E2 gene. Such validation might increase support for the theory that ovarian aging is partly due to aging of the vascular supply to the ovary.


METHODS
We used a random sample of 742 naturally postmenopausal women from a large population-based cross-sectional study. Data on age at natural menopause, smoking, body mass index, reproductive history, and other health factors were collected through questionnaires. We studied the association between single nucleotide polymorphisms in the genes encoding for coagulation factors II, V, and VII and the apolipoprotein E2 gene and age at natural menopause using linear regression analysis. We corrected for oral contraceptive use, parity, current smoking, and body mass index.


RESULTS
Only the heterozygous deletion/insertion mutation in clotting factor VII was significantly associated with an increase of menopausal age of 0.81 year (95% CI: 0.12-1.50 y). The homozygous variant, however, was not. The single nucleotide polymorphisms in the other genes studied were not significantly associated with age at natural menopause. Adjustment for various lifestyle factors did not change the associations between single nucleotide polymorphisms and age at menopause.


CONCLUSIONS
Earlier findings relating specific point mutations in cardiovascular risk factor genes with age of natural menopause could not be confirmed in the present study.
van Disseldorp
Jeroen
J
Department of Reproductive Medicine and Gynecology, University Medical Center Utrecht, Utrecht, The Netherlands.
Broekmans
Frank J
FJ
Peeters
Petra H
PH
Fauser
Bart C
BC
van der Schouw
Yvonne T
YT
D000375:Aging / Q000235:genetics; D053329:Apolipoprotein E2 / Q000235:genetics; D001779:Blood Coagulation Factors / Q000235:genetics*; D005260:Female; D006801:Humans; D008593:Menopause / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
D053329:Apolipoprotein E2; D001779:Blood Coagulation Factors