Carrillo-Cruz, EstrellaGarcia-Lozano, Jose RMarquez-Malaver, Francisco JSanchez-Guijo, Fermin MMontero-Cuadrado, IsabelFerra I Coll, ChristelleValcarcel, DavidLopez-Godino, OrianaCuesta, MarianParody, RocioLopez-Corral, LuciaAlcoceba, MiguelCaballero-Velazquez, TeresaRodriguez-Gil, AlfonsoBejarano-Garcia, Jose ALopes-Ramos, TeresaPerez-Simon, Jose A2023-01-252023-01-252019Carrillo-Cruz E, García-Lozano JR, Márquez-Malaver FJ, Sánchez-Guijo FM, Montero Cuadrado I, Ferra I, et al. Vitamin D Modifies the Incidence of Graft-versus-Host Disease after Allogeneic Stem Cell Transplantation Depending on the Vitamin D Receptor (VDR) Polymorphisms. Clin Cancer Res. 2019 Aug 1;25(15):4616-4623http://hdl.handle.net/10668/13898The 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.enCase-Control StudiesCholecalciferolGraft vs Host DiseaseHaplotypesHematopoietic Stem Cell TransplantationHumansIncidencePolymorphism, Single NucleotideProspective StudiesReceptors, CalcitriolSpainTreatment OutcomeVitaminsresearch article31043390Restricted AccessPolimorfismo de nucleótido simpleGenotipoDosificaciónTrasplante de células madreEnsayo clínico10.1158/1078-0432.CCR-18-38751557-3265