Hana Fakhoury

Vitamin D plays a crucial role in modulating the innate immune response by interacting with its intracellular receptor, VDR. In this review, we address vitamin D/VDR signaling and how it contributes to the regulation of intestinal and respiratory microbiota. We additionally review some components of the innate immune system, such as the barrier function of the pulmonary and intestinal epithelial membranes and secretion of mucus, with their respective modulation by vitamin D. We also explore the mechanisms by which this vitamin D/VDR signaling mounts an antimicrobial response through the transduction of microbial signals and the production of antimicrobial peptides that constitute one of the body’s first lines of defense against pathogens. Additionally, we highlight the role of vitamin D in clinical diseases, namely inflammatory bowel disease and acute respiratory distress syndrome, where excessive inflammatory responses and dysbiosis are hallmarks. Increasing evidence suggests that vitamin D supplementation may have potentially beneficial effects on those diseases.

Objectives Despite its wide usage, warfarin therapy remains challenging due to its narrow therapeutic index, inter-individual response variability, and risk of bleeding. Previous reports have suggested that polymorphisms in VKORC1 and CYP2C9 genes could influence warfarin therapy. Herein, we investigated whether VKORC1 −1173C>T, CYP2C9*2 , and CYP2C9*3 gene polymorphisms are associated with warfarin dose adjustment and related bleeding events. Methods This cross-sectional study was conducted on Saudi adults receiving warfarin for more than 1 month. Their demographics and relevant clinical data were obtained. Genotyping for VKORC1 −1173C>T, CYP2C9*2 , and CYP2C9*2 genotypes was performed. Results Patients who are homozygous for the mutant T allele VKORC1 T/T required the lowest warfarin daily maintenance dose, compared to VKORC1 C/T and VKORC1 C/C. Similarly, there was a significant reduction in warfarin daily maintenance dose among CYP2C9*1/*3 and CYP2C9*1/*2 groups compared to CYP2C9*1/*1 . However, we found no significant correlation between the studied polymorphisms and warfarin-associated bleeding. Conclusions Similar to other populations, the VKORC1 and CYP2C9 gene polymorphisms are significantly associated with warfarin dosage in Saudi patients. The presence of at least one copy of the mutant alleles for VKORC1 −1173C>T, CYP2C9*2 , and CYP2C9*3 is associated with a significant reduction in warfarin maintenance dose.