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

Abstract

AbstractPrimary 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.