Estrogen receptor α CA dinucleotide repeat polymorphism is associated with rate of bone loss in perimenopausal women and bone mineral density and risk of osteoporotic fractures in postmenopausal women

Abstract

The association between a newly identified CA repeat polymorphism of the estrogen receptor alpha gene (ESR1) with osteoporosis was investigated. Postmenopausal women with <18 CA repeats had low BMD, increased rate of bone loss and increased fracture risk. Introduction: Studies have shown that intronic dinucleotide repeat polymorphisms in some genes are associated with disease risk by modulating mRNA splicing efficiency. D6S440 is a newly identified intronic CA repeat polymorphism located downstream of the 5′-splicing site of exon 5 of ESR1. Methods: The associations of D6S440 with bone mineral density (BMD), rate of bone loss and fracture risk were evaluated in 452 pre-, 110 peri- and 622 postmenopausal southern Chinese women using regression models. Results: Post- but not premenopausal women with less CA repeats had lower spine and hip BMD. The number of CA repeats was linearly related to hip BMD in postmenopausal women (β=0.008; p=0.004). Postmenopausal women with CA repeats <18 had higher risks of having osteoporosis (BMD T-score<-2.5 at the spine: OR 2.46, 95% CI 1.30-4.65; at the hip: OR 3.79(1.64-8.74)) and low trauma fractures (OR 2.31(1.29-4.14)) than those with ≥18 repeats. Perimenopausal women with <18 CA repeats had significantly greater bone loss in 18 months at the hip than those with ≥18 repeats (-1.96% vs. -1.61%, p=0.029). Conclusions: ESR1 CA repeat polymorphism is associated with BMD variation, rate of bone loss and fracture risk, and this may be a useful genetic marker for fracture risk assessment. © International Osteoporosis Foundation and National Osteoporosis Foundation 2007.