Vitamin D Receptor Gene Polymorphisms and Risk of Knee Osteoarthritis: Possible Correlations with TNF-α, Macrophage Migration Inhibitory Factor, and 25-Hydroxycholecalciferol Status

Abstract

Osteoarthritis (OA) etiology and pathogenesis not yet fully understood. We studied the role of vitamin D receptor single-nucleotide polymorphisms (VDR-SNPs), vitamin D3, serum and synovial macrophage migration inhibitory factor (MIF), and tumor necrosis factor-α (TNF-α) in the development and progression of knee OA (KOA). This study included 205 Egyptian subjects (105 patients with KOA and 100 unrelated, healthy matched subjects selected as controls). The patient group was divided into three groups according to KOA severity (mild, moderate, and severe), with 35 patients in each group. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used for the ApaI and TaqI SNPs. Vitamin D, serum and synovial TNF-α, and MIF assays were performed using ELISA kits. There were significantly lower serum levels of 25-hydroxycholecalciferol with significant increasing TNF-α and MIF levels in relation to disease severity among the cases (all: p˂0.05).Wild homozygous and heterozygous mutant genotypes (GG+GT) and G allele of ApaI demonstrated risk for KOA development, with odds ratio OR = 6.313 (95% confidence interval (CI) 2.074-19.210) and OR = 1.532 (95%CI 1.013-2.317), respectively. Homozygous mutant CC genotype and C allele of TaqI could be considered a risk factor associated with KOA development, with OR = 2.667 (95%CI 1.270-5.601) and OR = 0.737 (95%CI 0.496-1.095), respectively. VDR-SNPs, vitamin D3, TNF-α, and MIF could play an essential role in the pathogenesis and progression of KOA with mechanistic associations.

Vitamin D Metabolic Pathway Components in Orthopedic Patientes—Systematic Review

“…In turn, Hassan et al (2022) [ 32 ] studied vitamin D receptor gene polymorphisms and the risk of osteoarthritis of the knee which may be correlated with TNF-α, a factor that inhibits macrophage migration (MIF), and 25-hydroxycholecalciferol concentration. The investigation included 205 participants which were assigned to the study (n = 105) and control group (n = 100).…”

“…Additionally, the homozygous mutant CC genotype and C allele of TaqI may be considered as a risk factor in correlation with KOA development. As a result of the obtained results, it was concluded that VDR-SNPs, vitamin D3, TNF-α, and MIF have a potential function in the pathogenesis and progression of KOA with mechanistic associations [ 32 ]. Table 1 presents the most important research about the vitamin D metabolic pathway in total knee arthroplasty.…”

Factors Modulating COVID-19: A Mechanistic Understanding Based on the Adverse Outcome Pathway Framework

“…There is a complex interplay between vitamin D and the immune response to viral infections. Low vitamin D status is proposed to induce upregulation of the TNF-α and downstream of NF–ĸB1 signaling pathway, which regulates inflammatory reactions toward viral infection in macrophages [ 407 , 408 ]. Vitamin D was shown as a potent suppressor of IFN-γ-mediated macrophages response, preventing the release of inflammatory cytokines and chemokines [ 409 ].…”