What question did this study set out to answer?

This research explores genetic variants in miR-155, MIR155HG, and TLR4 to understand their role in inflammatory joint diseases.

April 16, 2026Open Access

Molecular Analysis of miR-155 and MIR155HG Mutations in Conjunction with TLR4 Variants in Inflammatory Joint Disease

Key Points

This research explores genetic variants in miR-155, MIR155HG, and TLR4 to understand their role in inflammatory joint diseases.
Conducted a case-control study with 100 participants (50 osteoarthritis patients and 50 controls).
Performed genomic DNA analysis using PCR and Sanger sequencing.
Calculated allele frequencies and genotypes using Mutation Surveyor.
Identified structural impacts of TLR4 mutations using in silico tools.
Identified sixteen heterozygous variants in MIR155HG exon 3, most being population-specific.
Documented two novel variants in the miR-155 gene, each present at 7.1% allele frequency.
Discovered two rare TLR4 exon-3 variants, including a missense mutation that destabilizes the TLR4 protein.

Abstract

Inflammatory joint diseases, including osteoarthritis, are multifactorial disorders in which dysregulated innate immune signaling and non-coding RNA (ncRNA)-mediated regulation of gene expression play essential roles. MicroRNA-155 (miR-155), its host gene MIR155HG, and Toll-like receptor 4 (TLR4) form a tightly linked inflammatory signaling axis, yet their combined genetic variability in chronic joint inflammation remains insufficiently characterized. The aim of this study was to investigate genetic variants in MIR155HG exon 3, mature miR-155, and TLR4 exon 3 and assess their potential synergistic role in chronic inflammatory joint disease. A case–control study was conducted with 100 cases (50 osteoarthritis patients and 50 matched healthy controls). Genomic DNA was analysed using polymerase chain reaction (PCR) and Sanger sequencing. Variant alleles and genotypes were identified, and their allele frequencies and genotypes were calculated using Mutation Surveyor. Detected variants were compared with public databases, and in silico tools were used to estimate the structural impact of TLR4 missense mutations. Sixteen heterozygous variants were identified in MIR155HG exon 3, most of them novel and population-specific. Interestingly, the highest variant frequencies for MIR155HG exon 3 were observed at positions 12448G>GC and 12481T>TA (both 64.3%), followed by 12442T>TC (57.1%). Additionally, two novel variants were detected in the miR-155 gene (chr21:29,694,314 G>A and chr21:29,646,351 T>C), each present at an allele frequency of 7.1% and absent from current external variant databases. Moreover, two rare TLR4 exon-3 variants were identified; a synonymous variant, c.147C>A (Pro49Pro; rs375037549), and a missense mutation, c.148G>A (Asp50Asn; rs776561489). Notably, in silico analyses and molecular dynamic simulations indicated that the Asp50Asn (D50N) substitution destabilizes the TLR4 protein. Conclusion: Concurrent variants in MIR155HG, miR-155, and TLR4 suggest a convergent regulatory molecular axis that may contribute to disease susceptibility and inflammatory progression.

Molecular Analysis of miR-155 and MIR155HG Mutations in Conjunction with TLR4 Variants in Inflammatory Joint Disease

Key Points

Abstract

Cite This Study