TY - JOUR T1 - Association of oestrogen receptor α gene polymorphisms with postmenopausal bone loss, bone mass, and quantitative ultrasound properties of bone JF - Journal of Medical Genetics JO - J Med Genet SP - 240 LP - 246 DO - 10.1136/jmg.2004.023895 VL - 42 IS - 3 AU - O M E Albagha AU - U Pettersson AU - A Stewart AU - F E A McGuigan AU - H M MacDonald AU - D M Reid AU - S H Ralston Y1 - 2005/03/01 UR - http://jmg.bmj.com/content/42/3/240.abstract N2 - Background: The gene encoding oestrogen receptor α (ESR1) appears to regulate bone mineral density (BMD) and other determinants of osteoporotic fracture risk. Objective: To investigate the relation between common polymorphisms and haplotypes of the ESR1 gene and osteoporosis related phenotypes in a population based cohort of 3054 Scottish women. Results: There was a significant association between a common haplotype “px”, defined by the PvuII andXbaI restriction fragment length polymorphisms within intron 1 of the ESR1 gene, and femoral neck bone loss in postmenopausal women who had not received hormone replacement therapy (n = 945; p = 0.009). Annual rates of femoral neck bone loss were ∼14% higher in subjects who carried one copy of px and 22% higher in those who carried two copies, compared with those who did not carry the px haplotype. The px haplotype was associated with lower femoral neck BMD in the postmenopausal women (p = 0.02), and with reduced calcaneal broadband ultrasound attenuation (BUA) values in the whole study population (p = 0.005). There was no association between a TA repeat polymorphism in the ESR1 promoter and any phenotype studied, though on long range haplotype analysis subjects with a smaller number of TA repeats who also carried the px haplotype had reduced BUA values. Conclusions: The ESR1px haplotype is associated with reduced hip BMD values and increased rates of femoral neck bone loss in postmenopausal women. An association with BUA may explain the fact that ESR1 intron 1 alleles predict osteoporotic fractures by a mechanism partly independent of differences in BMD. ER -