Bone metabolism gene polymorphism and response to bisphosphonate treatment in women with postmenopausal osteoporosis

This repository contains the raw and source data for the manuscript "Bone metabolism gene polymorphism and response to bisphosphonate treatment in women with postmenopausal osteoporosis". <strong>Abstract: </strong>A response to bisphosphonates (BPs) therapy may be explained by influence of multiple factors, including genetic. The aim of this study was to analyze the association of <em>SOST</em>, <em>PTH</em>, <em>FGF2</em>, <em>FDPS</em>, <em>GGPS1</em>, and <em>LRP5</em> gene variants on the response to BPs treatment. In total, 208 women with at least 12 months of BPs therapy of postmenopausal osteoporosis were included in the study. All patients were divided into responders (118 subjects) and non-responders (90 subjects) according to BMD dynamics. As single markers, the <em>SOST</em> rs1234612 T/T (OR=1.8; P=0.018), <em>PTH</em> rs7125774 T/T (OR=2.9, P=0.0001), <em>FDPS</em> rs2297480 G/G (OR=25.9, P=1.5×10^-7), and <em>GGPS1</em> rs10925503 C/C+C/T (OR=3.0; P=0.0019) gene variants were over-represented in non-responders. No significant association was revealed for <em>FGF2</em> rs6854081 and <em>LRP5</em> rs3736228 variants. The carriers of T-T-G-C allelic combination (constructed from rs1234612, rs7125774, rs2297480, and rs10925503) were predisposed to negative response to BPs treatment (OR=4.6, 95% CI 1.7–13.0, P=0.004). The C-C-T-C combination was significantly over-represented in responders (15.8% <em>vs.</em> 3.0% in non-responders, P=0.002). Our findings highlight the importance of identified single gene variants and their allelic combinations for pharmacogenetics of BPs therapy of osteoporosis; the screening of these markers can be used as a new strategy for personalized antiresorptive therapy.