Vitamin D modifies the incidence of graft-versus-host disease after allogeneic stem cell transplantation depending on the Vitamin D Receptor (VDR) polymorphisms

Estrella Carrillo-Cruz, Jose R. García-Lozano, Francisco J. Marquez-Malaver, Fermín M. Sanchez-Guijo, Isabel Montero Cuadrado, Christelle Ferrai Coll, David Valcarcel, Oriana Lopez-Godino, Marian Cuesta, Rocío Parody, Lucía Lopez-Corral, Miguel Alcoceba, Teresa Caballero-Velazquez, Alfonso Rodríguez-Gil, Jose A. Bejarano-García, Teresa Lopes Ramos, Jose A. Perez-Simon*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)

Abstract

Purpose: The biologically active metabolite of Vitamin D3, 1,25-dihydroxyVitamin D3 (vit D), has immunoregulatory properties via binding Vitamin D receptor (VDR). In a prospective trial, we previously reported a reduction in the incidence of chronic GvHD (cGvHD) among patients who received vit D after allogeneic stem cell transplantation (allo-HSCT; Clinical Trials.gov: NCT02600988). Here we analyze the role of patients and donors' VDR SNPs on the immunomodulatory effect of vit D. Patients and Methods: Patients undergoing allo-HSCT were included in a prospective phase I/II clinical trial (Alovita) in three consecutive cohorts: Control (without vit D), low-dose (1,000 IU/day), and high-dose (5,000 IU/day) groups. Vit D was given from day -5 until +100 after transplant. Genotyping of four SNPs of the VDR gene, FokI, BsmI, ApaI, and TaqI, were performed using TaqMan SNP genotyping assays. Results: We observed a decrease in the incidence of overall cGvHD at 1 year after allo-HSCT depending on the use or not of vit D among patients with FokI CT genotype (22.5% vs 80%, P = 0.0004) and among those patients without BsmI/ApaI/TaqI ATC haplotype (22.2% vs 68.8%, P = 0.0005). In a multivariate analysis, FokI CT genotype significantly influenced the risk of cGvHD in patients treated with vit D as compared with the control group (HR 0.143, Pinteraction < 0.001). Conclusions: Our results show that the immunomodulatory effect of vit D depends on the VDR SNPs, and patients carrying the FokI CT genotype display the highest benefit from receiving vit D after allo-HSCT.

Original languageEnglish
Pages (from-to)4616-4623
Number of pages8
JournalClinical Cancer Research
Volume25
Issue number15
DOIs
Publication statusPublished - 1 Aug 2019
Externally publishedYes

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