A Polymorphism at the Translation Start Site of the Vitamin D Receptor Gene Is Associated with the Response to Anti-Osteoporotic Therapy in Postmenopausal Women from Southern Italy

International Journal of Molecular Sciences

Valeria Conti⁵  Giusy Russomanno⁹  Graziamaria Corbi⁴  Giuseppe Toro²  Vittorio Simeon¹  Walter Filippelli³  Nicola Ferrara⁷  Michela Grimaldi⁵  Valeria D𠆚rgenio⁶  Nicola Maffulli⁸  Amelia Filippelli⁵ 

[1] Laboratory of Pre-clinical and Translational Research, Reference Cancer Center of Basilicata, Scientific Institute of Hospitalization and Treatment, Rionero in Vulture 85028, Italy; E-Mail:;Unit of Orthopaedics and Traumatology, “Martiri del Villa Malta” Hospital, Sarno 84087, Italy; E-Mail:;Department of Studies for Institutions and Territorial Systems, University “Parthenope” of Naples, Naples 80133, Italy; E-Mail:;Department of Medicine and Health Sciences, University of Molise, Campobasso 86100, Italy;Department of Medicine and Surgery, University of Salerno, Baronissi 84081, Italy; E-Mails:;Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Naples 80131, Italy; E-Mail:;Department of Medical Translational Sciences, University of Naples Federico II, Naples 80131, Italy; E-Mail:;Department of Musculoskeletal Disorders, Faculty of Medicine and Surgery, University of Salerno, Baronissi 84081, Italy; E-Mail:;Doctoral School of Translational and Clinical Medicine, University of Salerno, Baronissi 84081, Italy; E-Mail:

关键词: pharmacogenetics;    postmenopausal osteoporosis;    bisphosphonate;    bone mineral density;    VDR genotype;    rs1544410;    rs2228570;   

DOI  :  10.3390/ijms16035452

来源: mdpi

【 摘 要 】

The present study investigated the effect of two single nucleotide polymorphisms (SNPs) of the vitamin D receptor (VDR) gene, rs1544410 A/G and rs2228570 C/T, in modulating bone mineral density (BMD) and the response to treatment with bisphosphonates or strontium ranelate in postmenopausal osteoporosis (PMO). Four hundred eighteen postmenopausal women from Southern Italy treated with bisphosphonates or strontium ranelate for three years were enrolled and stratified according to their genotype. Changes in BMD were expressed as the delta t-score (Δt-score). Allelic frequencies for rs1544410 A/GSNP were 11.2% AA, 50.0% GA and 38.8% GG; for rs2228570 C/TSNP were 54.8% CC, 39.5% TC and 5.7% TT. TT carriers showed a lower t-score than TC and CC (both p < 0.02) genotypes and were more responsive to the therapy when compared to both TC (p < 0.02) and CC (p < 0.05) carriers. Specifically, TT carriers receiving alendronate demonstrated a significant improvement of the Δt-score compared to TC and CC (both p < 0.0001) carriers. After adjustment for confounders, the Δt-score showed evidence of a statistically significant positive association with TT in all treatments considered. Therapy response was independent of rs1544410 A/G SNP; instead, rs2228570 C/TSNP was associated with a better response to antiresorptive treatment, thus suggesting that the therapy for PMO should be personalized.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.