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

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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.

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Data Availability

The datasets used and analyzed in this study are available upon reasonable request.

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Funding

This study was partially funded by the Faculty of Medicine, South Valley University, Qena 83523, Egypt.

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Authors and Affiliations

  1. Department of Medical Biochemistry, Faculty of Medicine, South Valley University, Qena, 83523, Egypt

    Mohammed H. Hassan

  2. Department of Orthopedic and Trauma Surgery, Faculty of Medicine, Al-Azhar University, Assiut Branch, Assiut, 71524, Egypt

    Amer Alkot Mostafa Elsadek

  3. Medical Physiology Department, Faculty of Medicine, Sohag University, Sohag, Egypt

    Marwa Ahmed Mahmoud

  4. Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut, 71524, Egypt

    Bakheet E. M. Elsadek

Authors
  1. Mohammed H. Hassan
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  2. Amer Alkot Mostafa Elsadek
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  3. Marwa Ahmed Mahmoud
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  4. Bakheet E. M. Elsadek
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Contributions

Study concept and design: MHH, AEME, MAM and BEME; Patient selection and clinical assessments: AEME; Blood sample collection and biochemical assays: MHH, BEME and MAM; Genetic assays and analyses: MHH, BEME and MAM; Statistical analysis: MHH, MAM and BEME; literature search: MHH: First manuscript draft: MMH. All authors revised and approved the final manuscript version.

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Correspondence to Mohammed H. Hassan.

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Conflict of Interest

The authors declare no conflicts of interest.

Ethical Approval

Cases and controls were included in the current research in accordance to the Declaration of Helsinki. The local University Hospital Ethics Committee, South Valley University, Qena, Egypt, has approved the current study (ethical approval code: SVU-MED-MBC004-4-21-1-111).

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Informed consent was obtained from all individual participants included in the study.

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Hassan, M.H., Elsadek, A.A.M., Mahmoud, M.A. et al. Vitamin D Receptor Gene Polymorphisms and Risk of Knee Osteoarthritis: Possible Correlations with TNF-α, Macrophage Migration Inhibitory Factor, and 25-Hydroxycholecalciferol Status. Biochem Genet 60, 611–628 (2022). https://doi.org/10.1007/s10528-021-10116-0

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