Potential Impact of Polymorphisms in Toll-like Receptors 2, 3, 4, 7, 9, miR-146a, miR-155, and miR-196a Genes on Osteoarthritis Susceptibility

Debora Stefik; Vladimir Vranic; Nemanja Ivkovic; Gordana Velikic; Dusan M Maric; Dzihan Abazovic; Danilo Vojvodic; Dusica L Maric; Gordana Supic

doi:10.3390/biology12030458

Potential Impact of Polymorphisms in Toll-like Receptors 2, 3, 4, 7, 9, miR-146a, miR-155, and miR-196a Genes on Osteoarthritis Susceptibility

Biology (Basel). 2023 Mar 16;12(3):458. doi: 10.3390/biology12030458.

Authors

Debora Stefik¹, Vladimir Vranic^{2

3}, Nemanja Ivkovic¹, Gordana Velikic⁴, Dusan M Maric⁴, Dzihan Abazovic⁵, Danilo Vojvodic^{1

3}, Dusica L Maric⁶, Gordana Supic^{1

3}

Affiliations

¹ Institute for Medical Research, Military Medical Academy, Crnotravska 17, 11000 Belgrade, Serbia.
² Clinic for Orthopedic Surgery and Traumatology, Military Medical Academy, Crnotravska 17, 11000 Belgrade, Serbia.
³ Medical Faculty of Military Medical Academy, University of Defense, Crnotravska 17, 11000 Belgrade, Serbia.
⁴ Department for Research and Development, Clinic Orto MD-Parks Dr Dragi Hospital, 21000 Novi Sad, Serbia.
⁵ Biocell Hospital, Omladinskih Brigada 86a, 11000 Belgrade, Serbia.
⁶ Department of Anatomy, Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia.

Abstract

Osteoarthritis (OA) is a progressive inflammatory disease of synovial joints and a leading cause of disability among adults. Inflammation-related genes, including genes for Toll-like receptors (TLRs), are tightly controlled by several microRNAs that, in addition to their pivotal role in the epigenetic regulation of target genes, are ligands for TLR activation and downstream signaling. Thus, we evaluated the association between OA risk and genetic variants in TLR2, TLR3, TLR4, TLR7, TLR9, and microRNAs that regulate TLRs signaling miR146a, miR155, and miR196a2. Our study group consisted of 95 surgically treated OA patients and a control group of 104 healthy individuals. Genetic polymorphisms were determined using TaqMan real-time PCR assays (Applied Biosystems). Adjusted logistic regression analysis demonstrated that polymorphisms in TLR4 rs4986790 (OR = 2.964, p = 0.006), TLR4 rs4986791 (OR = 8.766, p = 0.00001), and TLR7 rs385389 (OR = 1.579, p = 0.012) increased OA risk, while miR-196a2 rs11614913 (OR = 0.619, p = 0.034) was significantly associated with decreased OA risk. Our findings indicate that polymorphisms in the TLR4 and TLR7 genes might increase OA risk and suggest a novel association of miR-196a2 polymorphism with decreased OA susceptibility. The modulation of TLRs and miRNAs and their cross-talk might be an attractive target for a personalized approach to OA management.

Keywords: TLR4; TLR7; Toll-like receptors; miR-196a; microRNA; osteoarthritis; polymorphisms.

Grants and funding

This research received no external funding.