Differential Genetic Effects of ESR1 Gene Polymorphisms on Osteoporosis Outcomes

2orless.Conversely,wefoundsignificantreductions in fracture risk. In women homozygous for the absence of an XbaI recognition site, the adjusted odds of all fractures were reduced by 19% (odds ratio, 0.81 [95% CI, 0.710.93]; P=.002) and vertebral fractures by 35% (odds ratio, 0.65 [95% CI, 0.49-0.87]; P=.003). Effects on fractures were independent of BMD and unaltered in adjusted analyses. No significant effects on fracture risk were seen for PvuII and TA repeats. Conclusions ESR1 is a susceptibility gene for fractures, and XbaI determines fracture risk by mechanisms independent of BMD. Our study demonstrates the value of adequately powered studies with standardized genotyping and clinical outcomes in defining effects of common genetic variants on complex diseases.