Genetic Polymorphisms (ApaI, FokI, BsmI, and TaqI) of the Vitamin D Receptor (VDR) Influence the Natural History and Phenotype of Crohn’s Disease

Vitamin D receptor (VDR) single-nucleotide polymorphisms (SNPs) modulate vitamin D/VDR signaling, a key pathway in inflammatory bowel disease (IBD) pathogenesis. This study investigates how ApaI, BsmI, TaqI, and FokI SNPs affect IBD phenotype and progression. A total of 76 Crohn's disease (CD) and 68 ulcerative colitis (UC) patients were genotyped. On initial bivariate analysis, the AA genotype of ApaI was accompanied by higher rates of penetrating (B3) CD (36.7% vs. 8.7%; <i>p</i> = 0.012). The FokI SNP was associated with disease location, with the ff genotype predisposing to CD and affecting the upper GI (36.4% vs. 7.7%; <i>p</i> = 0.044) or the colon (90.9% vs. 50.8%; <i>p</i> = 0.038). Moreover, patients harboring the ApaI A allele (AA/Aa) experienced higher rates of steroid-refractory or steroid-dependent CD. In multivariate analyses, the aa genotype showed a protective effect against hospitalization (aOR = 0.17; <i>p</i> = 0.013) in CD, whereas the TT genotype emerged as an independent risk factor (aOR = 4.79; <i>p</i> = 0.044). Moreover, the aa genotype was independently associated with a decreased risk of IBD-related surgery (aOR = 0.055; <i>p</i> = 0.014). VDR SNPs, particularly ApaI, influence disease phenotype, progression, and treatment response in CD. The aa genotype of ApaI appears to confer protection against adverse disease outcomes.