Alleles of the estrogen receptor alpha-gene and an estrogen receptor cotranscriptional activator gene, amplified in breast cancer-1 (AIB1), are associated with quantitative calcaneal ultrasound

Quantitative bone ultrasound (QUS) has a significant heritable component. B ecause estrogen is required for attainment of peak bone mass, we studied al leles of two genes, estrogen receptor cr (ERI) and amplified in breast canc er-1 (AIB1), for their association with QUS, In a volunteer sample of 663 w hite women aged 18-35 years, bone ultrasound attenuation (BUA), Speed of so und (SOS), and heel stiffness index (SI), the latter consisting of the comp onent measures of BUA and SOS, were measured at the right calcaneus by QUS, Subjects were genotyped for the ERI polymorphisms Xba I and Pvu II and for the AIB1 polyglutamine tract polymorphism. In a multiple regression analys is, ERI genotype was an independent predictor of QUS-SI (p = 0.03), Because AIB1 and ERI enhance gene expression in a coordinate manner, we also searc hed for interactions. A gene-by-gene interaction effect was seen for QUS-SI (p = 0.009), QUS-BUA (p = 0.03), and QUS-SOS (p = 0.004). These remained s ignificant after the inclusion of clinically relevant variables into the fi nal regression model, Overall, these clinical and genetic factors accounted for up to 16% of the variance in peak QUS; the genetic markers alone accou nted for 4-7%, This is the first demonstration of specific genetic effects on calcaneal QUS encoded by alleles of genes directly involved in mediating estrogen effects on bone.