Role of CYP24A1, VDR and GC gene polymorphisms on deferasirox pharmacokinetics and clinical outcomes

β-Thalassemia patients develop deficiency in vitamin D absorption and liver hydroxylation, resulting in extremely low calcitriol levels. We explored the role of single-nucleotide polymorphisms (SNPs) involved in vitamin D metabolism, transport and activity on deferasirox pharmacokinetics and outcomes (effectiveness trough levels (C_trough) and the area under the curve (AUC) cutoffs of 20 μg ml^-1 and 360 μg ml^-1 h^-1, respectively; nonresponse AUC limit of 250 μg ml^-1 h^-1). Ninety-nine β-thalassemic patients were enrolled. Drug plasma C_trough and AUC were measured by the high-performance liquid chromatography system coupled with an ultraviolet determination method. Allelic discrimination for VDR, CYP24A1, CYP27B1 and GC gene SNPs was performed by real-time PCR. CYP24A1 22776 TT significantly influenced C_min and negatively predicted it in regression analysis. CYP24A1 3999 CC was associated with C_trough and C_min and was a negative predictor of T_max, whereas CYP24A1 8620 GG seemed to have a role in C_trough, AUC, t_1/2 and C_min, and was an AUC negative predictor factor. Considering treatment outcome, Cdx2 and GC 1296 were retained in regression analysis as AUC efficacy cutoff negative predictors.