Genetic variants in the retinoid X receptor gene contribute to osteoarthritis susceptibility

Authors

  • Debora Štefik Institute for Medical Research, Military Medical Academy, Crnotravska 17, 11000 Belgrade, Serbia https://orcid.org/0000-0001-6610-4812
  • Vladimir Vranić Clinic for Orthopedic Surgery and Traumatology, Military Medical Academy, Crnotravska 17, 11000 Belgrade, Serbia
  • Nemanja Ivković Institute for Medical Research, Military Medical Academy, Crnotravska 17, 11000 Belgrade, Serbia https://orcid.org/0000-0001-8982-8848
  • Biljana Božić Nedeljković Faculty of Biology, University of Belgrade, Studentski trg 3, 11000 Belgrade, Serbia https://orcid.org/0000-0002-1238-1731
  • Gordana Šupić 1. Institute for Medical Research, Military Medical Academy, Crnotravska 17, 11000 Belgrade, Serbia; 2. Medical Faculty of Military Medical Academy, University of Defense, 11000 Belgrade, Serbia https://orcid.org/0000-0003-0350-4733

DOI:

https://doi.org/10.2298/ABS240306010S

Keywords:

retinoid X receptor (RXR), polymorphism, osteoarthritis, inflammation

Abstract

Paper description:

  • Osteoarthritis, a progressive joint disease characterized by persistent inflammation, has both hereditary and environmental causes.
  • This study is the first to examine the association between osteoarthritis and polymorphisms in the RXRα gene, which regulates inflammatory pathways and acts as a transcriptional partner of vitamin D3 and retinoic acid receptors.
  • The RXRα polymorphism rs7864987 is associated with an increased risk of osteoarthritis (P=0.012), while rs3118523 reduces its risk (P=0.030).
  • RXRα is an inflammation-related gene involved in the complex network underlying the immunopathology of osteoarthritis, and its polymorphisms could potentially drive individualized retinoid therapy for osteoarthritis.

Abstract: Osteoarthritis (OA) is a progressive disease of the joints that causes a gradual loss of function, resulting in limited mobility. Chronic inflammation is the main molecular process that triggers and propagates this disease. The retinoid X receptor (RXR), a member of the nuclear receptor family, is involved in modulating inflammatory pathways by influencing key pro-catabolic inflammatory cytokines, chemokines, and enzymes responsible for instigating and sustaining chronic joint inflammation. We evaluated the association between OA risk and genetic variants in the RXRα isoform. Compared to control individuals, a statistically significant difference in genotype distribution was detected for the rs7864987 polymorphism (P=0.008), while a positive inclination toward association was noted for rs3118523 (P=0.077). According to our findings based on the additive model, it appears that RXRα rs7864987 is linked to a higher risk of OA (adjusted odds ratio (OR)=1.846, P=0.012), whereas rs3118523 is associated with decreased risk of OA (adjusted OR=0.569, P=0.030). These results suggest that RXRα could be a significant inflammation-related gene involved in the complex network underlying the immunopathology of osteoarthritis. RXRα polymorphisms could potentially drive individualized retinoid therapy for OA based on genetic profile.

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2024-07-10

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1.
Štefik D, Vranić V, Ivković N, Božić Nedeljković B, Šupić G. Genetic variants in the retinoid X receptor gene contribute to osteoarthritis susceptibility . Arch Biol Sci [Internet]. 2024Jul.10 [cited 2024Jul.18];76(2):151-60. Available from: https://serbiosoc.org.rs/arch/index.php/abs/article/view/9618

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Vol. 76 No. 2 (2024)

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Copyright (c) 2024 Debora Štefik, Vladimir Vranić, Nemanja Ivković, Biljana Božić Nedeljković, Gordana Šupić

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