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Supplementary Data from Vitamin D Modifies the Incidence of Graft-versus-Host Disease after Allogeneic Stem Cell Transplantation Depending on the Vitamin D Receptor (VDR) Polymorphisms

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posted on 2023-03-31, 21:06 authored by Estrella Carrillo-Cruz, José R. García-Lozano, Francisco J. Márquez-Malaver, Fermín M. Sánchez-Guijo, Isabel Montero Cuadrado, Christelle Ferra i Coll, David Valcárcel, Oriana López-Godino, Marian Cuesta, Rocío Parody, Lucía López-Corral, Miguel Alcoceba, Teresa Caballero-Velázquez, Alfonso Rodríguez-Gil, José A. Bejarano-García, Teresa Lopes Ramos, José A. Pérez-Simón

Supplementary table 2. VDR genotype and haplotype frequencies.

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CIBERONC

Instituto de Salud Carlos III

Ministerio de sanidad y política social

ISCIII

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ARTICLE ABSTRACT

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 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. 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). 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.

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