%0 Journal Article
%A Carrillo-Cruz, Estrella
%A Garcia-Lozano, Jose R
%A Marquez-Malaver, Francisco J
%A Sanchez-Guijo, Fermin M
%A Montero-Cuadrado, Isabel
%A Ferra I Coll, Christelle
%A Valcarcel, David
%A Lopez-Godino, Oriana
%A Cuesta, Marian
%A Parody, Rocio
%A Lopez-Corral, Lucia
%A Alcoceba, Miguel
%A Caballero-Velazquez, Teresa
%A Rodriguez-Gil, Alfonso
%A Bejarano-Garcia, Jose A
%A Lopes-Ramos, Teresa 
%A Perez-Simon, Jose A
%T Vitamin D Modifies the Incidence of Graft-versus-Host Disease after Allogeneic Stem Cell Transplantation Depending on the Vitamin D Receptor (VDR) Polymorphisms.
%D 2019
%U http://hdl.handle.net/10668/13898
%X 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  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.
%K Case-Control Studies
%K Cholecalciferol
%K Graft vs Host Disease
%K Haplotypes
%K Hematopoietic Stem Cell Transplantation
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