ASSOCIATION OF BONE-MINERAL DENSITY WITH POLYMORPHISM OF THE ESTROGEN-RECEPTOR GENE

PvuII and XbaI restriction fragment length polymorphisms (RFLPs) of th e estrogen receptor (ER) gene and its relation to bone mineral density (BMD) were examined in 238 postmenopausal healthy women aged 45-91 ye ars (66.3 +/- 0.6 years, mean +/- standard error of the mean [SEM]) in Japan, The RFLPs were represented as Pp (PvuII) and Xx (XbaI), with c apital letters signifying the absence of and small letters the presenc e of restriction sites, In the PPxx genotype (n = 18), Z score values of BMD were significantly lower than those for other genotypes (n = 22 0) (lumbar spine, -0.746 vs. -0.065 [p = 0.022]; total body, -0.482 vs . 0.308 [p = 0.002]), We classified the subjects into three genotypes with allelic haplotype: homozygote of the Px haplotype was expressed a s the 11 genotype, heterozygote of the Px haplotype as the 10 genotype , and the one lacking the Px haplotype as the 00 genotype, The PpXx ge notype,vas not included in this analysis because the allelic haplotype s are uncertain, The Px haplotype was associated with a low BMD in pos tmenopausal women (Z score for the lumbar spine, -0.746 vs. -0.279 vs. 0.083, for the 11, 10, 00 genotypes, respectively [p = 0.029]; Z scor e for the total body, -0.482 vs. 0.164 vs, 0.427, respectively [p = 0. 003]), We suggest that some variation of the ER gene linked to these R FLPs is associated with low BMD and that this at least partly explains the cause of postmenopausal osteoporosis in Japanese women.