Human Reproduction, Vol. 19, No. 1, 59-64,
January 2004
© 2004 European Society of Human Reproduction and Embryology
Effects of vitamin D and estrogen receptor gene polymorphisms on the changes in lumbar bone mineral density with multiple pregnancies in Japanese women
Department of Obstetrics and Gynecology, Niigata University School of Medicine, 1-757 Asahimachi-dori, Niigata 951-8510, Japan
1 To whom correspondence should be addressed. e-mail: takumi{at}med.niigata-u.ac.jp
BACKGROUND: Our aims were to follow the longitudinal changes in lumbar spine bone mineral density (BMD) with multiple pregnancies, and to study whether polymorphisms in the vitamin D receptor (VDR) and estrogen receptor (ER) genes may influence the results. METHODS: We repeatedly measured the BMD of the lumbar spine (L2L4) of 133 women who had undergone two successive pregnancies and 73 non-pregnant controls, and analysed the restriction fragment length polymorphisms using restriction endonucleases TaqI, ApaI and FokI for the VDR gene, and PvuII and XbaI for the ER gene. RESULTS: Cases and controls had no significant differences in the longitudinal BMD changes. The mean percentage change in lumbar BMD (
BMD%) of the women with the XX/Xx genotype was significantly lower than that of the women with the xx genotype after adjusting for age at each delivery, BMD of the first scan, and interval between the scans (0.2 ± 3.3 versus 2.0 ± 4.2%; P = 0.030, analysis of covariance). Multiple regression analyses to evaluate the contribution of the XbaI polymorphism of the ER gene on
BMD% showed that the percentage decrease in BMD was greater for women lacking the XbaI restriction site (adjusted R2 = 0.188, P < 0.0001). CONCLUSIONS: The present study suggests that the
BMD% was significantly influenced by the XbaI polymorphism of the ER gene.
Key words: bone mineral density/estrogen receptor/genetic polymorphism/pregnancy/vitamin D receptor
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