Kafentzi Theodora, Tsounis Efthymios P, Tourkochristou Evanthia, Avramopoulou Evdoxia, Aggeletopoulou Ioanna, Geramoutsos Georgios, Sotiropoulos Christos, Pastras Ploutarchos, Thomopoulos Konstantinos, Theocharis Georgios, Triantos Christos
Division of Gastroenterology, Department of Internal Medicine, Medical School, University of Patras, 26504 Patras, Greece.
Int J Mol Sci. 2025 Feb 21;26(5):1848. doi: 10.3390/ijms26051848.
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%; = 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%; = 0.044) or the colon (90.9% vs. 50.8%; = 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; = 0.013) in CD, whereas the TT genotype emerged as an independent risk factor (aOR = 4.79; = 0.044). Moreover, the aa genotype was independently associated with a decreased risk of IBD-related surgery (aOR = 0.055; = 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.
维生素D受体（VDR）单核苷酸多态性（SNP）可调节维生素D/VDR信号传导，这是炎症性肠病（IBD）发病机制中的关键途径。本研究调查了ApaI、BsmI、TaqI和FokI SNP如何影响IBD的表型和病程。对总共76例克罗恩病（CD）患者和68例溃疡性结肠炎（UC）患者进行了基因分型。在初始双变量分析中，ApaI的AA基因型与穿透性（B3）CD的发生率较高相关（36.7%对8.7%；P = 0.012）。FokI SNP与疾病部位相关，ff基因型易患CD并累及上消化道（36.4%对7.7%；P = 0.044）或结肠（90.9%对50.8%；P = 0.038）。此外，携带ApaI A等位基因（AA/Aa）的患者发生类固醇难治性或类固醇依赖性CD的几率更高。在多变量分析中，aa基因型对CD患者住院具有保护作用（校正优势比[aOR]=0.17；P = 0.013），而TT基因型是独立危险因素（aOR = 4.79；P = 0.044）。此外，aa基因型与IBD相关手术风险降低独立相关（aOR = 0.055；P = 0.014）。VDR SNP，尤其是ApaI SNP，影响CD的疾病表型发生率、病程和治疗反应。ApaI的aa基因型似乎对不良疾病结局具有保护作用。
