Association of estrogen receptor beta gene polymorphisms and rate of bone loss in perimenopausal women

Abstract

Estrogen deficiency associated with menopause is a major cause of osteoporosis in women. Understanding the pathogenesis of bone loss associated with menopause and early identification of perimenopausal women with rapid bone loss is an effective approach to help reduce the increasing incidence of osteoporosis. To determine the role of estrogen receptor beta gene (ESR2) and rate of bone loss in perimenopausal women, we studied 12 single nucleotide polymorphisms (SNPs) encompassing the whole ESR2 gene in 269 Southern Chinese women aged 40--60 years (mean age 49.8± 3.6). Bone mineral density (BMD) was measured at a mean interval of 18months (range 12--24 months). The association and risk of rapid bone loss (3% per annum) with ESR2 SNP and SNP haplotype was assessed using chi-square test and logistic regression model. The results showed that allele C carriers at a SNP in the promoter region (nt -1213 TC) was associated with lower risk of rapid bone loss at both the spine and hip (lumbar spine OR=0.47, p=0.023, femoral neck OR=0.47, p=0.017, trochanter: OR=0.053, p=0.041 and total hip OR=0.41, p=0.005). When adjusted for age, height and body weight, all sites remained significant (lumbar spine: OR=0.47, p=0.023, femoral neck: OR=0.47, p =0.017; total hip: OR=0.41, p=0.005). Analysis of the haplotype data revealed similar findings as individual SNP analysis. In conclusion, SNP and SNP haplotype of ESR2 is associated with rate of bone loss in perimenopausal women and may be useful for predicting bone loss during early postmenopausal period.