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

Valeria Conti, Giusy Russomanno, Graziamaria Corbi, Giuseppe Toro, Vittorio Simeon, Walter Filippelli, Nicola Ferrara, Michela Grimaldi, Valeria D’Argenio, Nicola Maffulli, Amelia Filippelli

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)5452-5466
Number of pages15
JournalInternational Journal of Molecular Sciences
Volume16
Issue number3
DOIs
Publication statusPublished - Mar 10 2015

Keywords

  • Bisphosphonate
  • Bone mineral density
  • Pharmacogenetics
  • Postmenopausal osteoporosis
  • Rs1544410
  • Rs2228570
  • VDR genotype

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Spectroscopy
  • Inorganic Chemistry
  • Catalysis
  • Molecular Biology
  • Computer Science Applications

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  • Cite this

    Conti, V., Russomanno, G., Corbi, G., Toro, G., Simeon, V., Filippelli, W., Ferrara, N., Grimaldi, M., D’Argenio, V., Maffulli, N., & Filippelli, A. (2015). 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, 16(3), 5452-5466. https://doi.org/10.3390/ijms16035452