Background: Total hip replacement (THR) significantly improves patients’ quality of life; however, prosthesis loosening remains a significant complication. Vitamin D, essential for calcium homeostasis and bone mineralization, is transported and stabilized by vitamin D binding protein (VDBP). Common single nucleotide polymorphisms (SNPs) in the VDBP gene, rs4588 and rs7041, may influence serum vitamin D levels and potentially impact THR outcomes. This study aimed to analyze the association between these SNPs, serum levels of VDBP and 25(OH)D, and their potential roles in THR outcomes. Methods: The study included three patient groups: (1) patients undergoing arthroscopy after a THR without prosthesis loosening (CA—Control Arthroplasty), (2) patients with hip prosthesis loosening (L—Loosening), and (3) a control group (C—Control). Genotyping of rs4588 and rs7041 in the VDBP gene was conducted using PCR-RFLP and TaqMan Genotyping real-time PCR. Serum levels of VDBP and 25(OH)D were measured using ELISA. Comparisons between groups were performed using statistical analyses, including odds ratios (OR) and significance testing (p-values). Results: There are significant differences in VDBP concentrations between the groups: L vs. CA (p < 0.0001), L vs. C (p = 0.0118), L vs. L + CA (p = 0.0013), CA vs. C (p < 0.0001), and CA vs. L + CA (p < 0.0001), and in 25(OH)D concentrations between groups: L vs. C (p < 0.0001), CA vs. C (p = 0.0008), and C vs. L + CA (p < 0.0001). Conclusions: The study findings suggest a protective role of 25(OH)D against prosthesis loosening in THR. The rs4588 SNP in the VDBP gene may increase the risk of loosening, while differences in VDBP and 25(OH)D concentrations between patient groups highlight their potential importance in THR outcomes.
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