Estrogen receptor α polymorphism as a genetic marker for bone loss, vertebral fractures and susceptibility to estrogen

Objective: The purpose of the present study was to investigate the possible roles of Null and XbaI polymorphisms of the estrogen receptor alpha (ERalpha) in bone mineral density (BMD), vertebral fracture, bone loss rate after menopause and response to hormone replacement therapy (HRT). Methods: All 286 women were grouped according to the genotypes of PnuuII or XbaI polymorphisms of the ERa gene. We compared the BMD Z-score, incidence of vertebral fracture, changes in Z-score after menopause and response of BMD to HRT among the genotypes. Results: Subjects with the PPxx genotype had significantly (P < 0.05) lower Z-scores than did subjects with the other genotypes. A negative correlation was observed between the length of time after menopause and the decrease of the Z-score only in women with the pp genotype, suggesting faster bone loss in this group. In the analysis of the ERa polymorphism with regard to the effect of HRT on BNID, there appears to be a significantly greater increase of BNID (P < 0.01 and 0.05) in women with the pp genotype than in those with the Pp or PP genotype. Conclusions: PnuuII and XbaI polymorphisms of the ERalpha gene were associated with BMD in postmenopausal Japanese women. Also, the polymorphisms may be useful genetic markers for predicting vertebral fracture in relatively young postmenopausal women. The,PvuII polymorphism may be associated with susceptibility to changes in estrogen level. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.