Association of Vitamin D Receptor (VDR) Gene BSMI polymorphism with inflammatory bowel disease in Iraqi Patients: A Case-Control Study

Background: The inflammatory bowel disease (IBD) that includes ulcerative colitis (UC) and Crohn disease (CD) is associated with complex interactions between genetic, environmental and immunological factors. Emerging evidence highlights an important role of vitamin D signaling in the regulation of intestinal immune homeostasis, with the Polymorphisms in the Vitamin D Receptor (VDR) gene having the potential to alter the disease susceptibility. This case-control study investigated the relationship between VDR Smi (rs1544410) polymorphism and IBD in an Iraqi population, and evaluated corresponding biochemical markers such as serum vitamin D₃ and C-reactive protein (CRP).

Methods: Eighty participants were enrolled, consisting of 40 clinically confirmed IBD patients (28 UC and 12 CD) and 40 healthy, age-matched controls. Genetic DNA was obtained via peripheral blood and 265 bp fragment of VDR gene was amplified through PCR, and restriction fragment length polymorphism was performed through data digestion using Smi enzyme to identify genotypes. Biochemical profiling was done by measuring serum vitamin D₃, CRP, glucose, hemoglobin, and calcium. Statistical analyses included chi-square tests, t -tests, Hardy-Weinberg analysis, and ROC curve analysis.

Results: Genotype distribution of the Smi polymorphism differed significantly between groups.  Bb and bb genotypes had a significant relationship with increased IBD as compared to the BB genotype, giving odds ratios of 7.28 and 26.71 respectively. The frequency of minor b allele was higher in the patient (33.7%), compared to the control (8.8%). The level of serum vitamin D₃ was significantly lower in patients, with significantly higher CRP and glucose. The ROC analysis showed superior diagnostic performance for vitamin D₃ (AUC 0.912, Sensitivity 87.5%, specificity 85.0%) compared to CRP (AUC 0.710).

Conclusion: The findings of the study indicate that VDR Smi polymorphism is a genetic predisposing factor to IBD in the Iraqi population and it is associated with significant biochemical changes, which substantiates the importance of vitamin D mechanisms in the pathogenesis of the disease and possible clinical monitoring.