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Int. J. Mol. Sci. 2015, 16(3), 5452-5466; doi:10.3390/ijms16035452

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

1
Department of Medicine and Surgery, University of Salerno, Baronissi 84081, Italy
2
Doctoral School of Translational and Clinical Medicine, University of Salerno, Baronissi 84081, Italy
3
Department of Medicine and Health Sciences, University of Molise, Campobasso 86100, Italy
4
Unit of Orthopaedics and Traumatology, "Martiri del Villa Malta" Hospital, Sarno 84087, Italy
5
Laboratory of Pre-clinical and Translational Research, Reference Cancer Center of Basilicata, Scientific Institute of Hospitalization and Treatment, Rionero in Vulture 85028, Italy
6
Department of Studies for Institutions and Territorial Systems, University "Parthenope" of Naples, Naples 80133, Italy
7
Department of Medical Translational Sciences, University of Naples Federico II, Naples 80131, Italy
8
Maugeri Foundation, Scientific Institute of Telese, IRRCS, Telese Terme 82037, Italy
9
Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Naples 80131, Italy
10
Department of Musculoskeletal Disorders, Faculty of Medicine and Surgery, University of Salerno, Baronissi 84081, Italy
11
Centre for Sports and Exercise Medicine, Barts and the London School of Medicine and Dentistry, Mile End Hospital, 275 Bancroft Road, London E1 4DG, UK
These authors contributed equally to this work.
This author is deceased during the study.
*
Author to whom correspondence should be addressed.
Academic Editor: Gloria Ravegnini
Received: 17 December 2014 / Revised: 17 February 2015 / Accepted: 4 March 2015 / Published: 10 March 2015
(This article belongs to the Special Issue Pharmacogenetics and Personalized Medicine)
View Full-Text   |   Download PDF [688 KB, uploaded 10 March 2015]

Abstract

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. View Full-Text
Keywords: pharmacogenetics; postmenopausal osteoporosis; bisphosphonate; bone mineral density; VDR genotype; rs1544410; rs2228570 pharmacogenetics; postmenopausal osteoporosis; bisphosphonate; bone mineral density; VDR genotype; rs1544410; rs2228570
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Conti, V.; Russomanno, G.; Corbi, G.; Toro, G.; Simeon, V.; Filippelli, W.; Ferrara, N.; Grimaldi, M.; D'Argenio, V.; Maffulli, N.; Filippelli, A. 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. Int. J. Mol. Sci. 2015, 16, 5452-5466.

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