Indirect influence of microRNA-146a on the association of IL-6 and TNF-α genetic polymorphisms with the increased risk of hip osteoarthritis

Karlo Tudor; Jurica Baranasic; Jelena Knezevic; Marta Serer Vicevic; Maja Sutic; Zlatko Dembic; Zdravko Jotanovic

doi:10.1002/jor.25804

Indirect influence of microRNA-146a on the association of IL-6 and TNF-α genetic polymorphisms with the increased risk of hip osteoarthritis

J Orthop Res. 2024 Feb 11. doi: 10.1002/jor.25804. Online ahead of print.

Authors

Karlo Tudor^{1

2}, Jurica Baranasic³, Jelena Knezevic³, Marta Serer Vicevic⁴, Maja Sutic³, Zlatko Dembic⁵, Zdravko Jotanovic^{1

2}

Affiliations

¹ Department for Orthopaedics and Physical medicine, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
² Orthopaedic Department, University Hospital for Orthopaedics and Traumatology Lovran, Lovran, Croatia.
³ Department for Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia.
⁴ Clinical Hospital Center Rijeka, Clinical Institute for Transfusion Medicine, Rijeka, Croatia.
⁵ Faculty of Dentistry, Institute of Oral Biology, University of Oslo, Oslo, Norway.

PMID: 38341771
DOI: 10.1002/jor.25804

Abstract

Primary osteoarthritis (POA) is a complex hereditary disease that involves the interplay between genetics and epigenetics. MicroRNA molecules play important roles in epigenetic mechanisms. MicroRNA-146a (miR-146a) is a negative regulator of the immune response in osteoarthritis (OA). So, variations in the miR-146a gene could affect OA risk. The aim of this study was to investigate the relationships between single nucleotide polymorphisms (SNPs) in the miR-146a, interleukin-6 (IL-6), Toll-like receptor 10 (TLR10), and tumor necrosis factor-alpha (TNFA) genes and the risk for development of advanced-stage primary hip osteoarthritis (PHOA) and primary knee osteoarthritis (PKOA) in the Croatian population. A total of 609 POA patients and 656 healthy donors were genotyped for SNPs in the miR-146a (rs2910164, G>C). Since we used same patients and controls as two studies before us, we already had information about IL-6 (rs1800795, C>G), TLR10 (rs11096957, C>T), and TNFA (rs1800629, C>T) genotypes of our subjects. None of the differences were statistically significant comparing either allelic or genotypic frequencies of miR-146a SNP rs2910164 (G>C) between the PHOA and PKOA patients and controls. However, we found a significant association with risk to PHOA for the combination of genotypes (stratified miR-146a genotype with the IL-6, and stratified miR-146a genotype with the TNFA). In a multifactorial disease such as POA, we have shown the indirect relevance of a second modifying factor (miR-146a), which apparently contributes to the overall risk of PHOA. There was no risk association with the PKOA, indicating that these two localities (hip and knee) might have different risk-modifying factors.

Keywords: genetic predisposition to disease; hip; knee; osteoarthritis.