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March 10, 2015International Journal of Molecular Sciences136 citationsOpen Access

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

VCValeria ContiGRGiusy RussomannoGCGraziamaria Corbi

Key Points

  • To investigate whether two vitamin D receptor (VDR) single nucleotide polymorphisms, rs1544410 and rs2228570, modulate bone mineral density and therapeutic response to bisphosphonates or strontium ranelate in postmenopausal osteoporosis.
  • Enrolled 418 postmenopausal women from Southern Italy undergoing 3 years of treatment with bisphosphonates or strontium ranelate.
  • Genotyped participants for VDR gene SNPs rs1544410 A/G and rs2228570 C/T and quantified bone mineral density changes using delta t-scores (Δt-score).
  • Carriers of the rs2228570 TT genotype exhibited significantly lower baseline t-scores than TC and CC carriers (both p < 0.02) but achieved greater treatment responsiveness compared to TC (p < 0.02) and CC (p < 0.05) genotypes.
  • TT carriers treated specifically with alendronate demonstrated marked improvement in Δt-scores compared to TC and CC carriers (both p < 0.0001), maintaining a significant positive association across all therapies after adjusting for confounders.
  • Therapeutic response showed no association with the rs1544410 A/G polymorphism.

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.

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Cite This Study

Conti et al. (2015) studied this question.

synapsesocial.com/papers/6a16f87d1375058a29059495https://doi.org/10.3390/ijms16035452
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