{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T12:00:06Z","timestamp":1776168006382,"version":"3.50.1"},"reference-count":68,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>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\u2013control 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&gt;GC and 12481T&gt;TA (both 64.3%), followed by 12442T&gt;TC (57.1%). Additionally, two novel variants were detected in the miR-155 gene (chr21:29,694,314 G&gt;A and chr21:29,646,351 T&gt;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&gt;A (Pro49Pro; rs375037549), and a missense mutation, c.148G&gt;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.<\/jats:p>","DOI":"10.3390\/cimb48040400","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T10:29:08Z","timestamp":1776162548000},"page":"400","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular Analysis of miR-155 and MIR155HG Mutations in Conjunction with TLR4 Variants in Inflammatory Joint Disease"],"prefix":"10.3390","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6853-4282","authenticated-orcid":false,"given":"Wissam Albeer","family":"Nooh","sequence":"first","affiliation":[{"name":"Department of Biology, College of Education for Pure Sciences, University of Al-Hamdaniya, Mosul 41002, Iraq"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9886-9868","authenticated-orcid":false,"given":"Raya Kh.","family":"Yashooa","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Education for Pure Sciences, University of Al-Hamdaniya, Mosul 41002, Iraq"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3144-0965","authenticated-orcid":false,"given":"Abdullah W.","family":"Khaleel","sequence":"additional","affiliation":[{"name":"Cancer Research and Hereditary Blood Diseases, Technical Research Center, Northern Technical University, Mosul 41001, Iraq"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0706-4658","authenticated-orcid":false,"given":"Treska S.","family":"Hassan","sequence":"additional","affiliation":[{"name":"General Directorate of Scientific Research Center, Salahaddin University-Erbil, Erbil 44001, Iraq"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5934-4465","authenticated-orcid":false,"given":"Shawnim M.","family":"Maaruf","sequence":"additional","affiliation":[{"name":"General Directorate of Scientific Research Center, Salahaddin University-Erbil, Erbil 44001, Iraq"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Safa M.","family":"Salim","sequence":"additional","affiliation":[{"name":"Cancer Research and Hereditary Blood Diseases, Technical Research Center, Northern Technical University, Mosul 41001, Iraq"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1742-6350","authenticated-orcid":false,"given":"Abd Al-Bar","family":"Al-Farha","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Food Sciences, Technical Agricultural College-Mosul, Northern Technical University, Mosul 41001, Iraq"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6774-2979","authenticated-orcid":false,"given":"Suhad A.","family":"Mustafa","sequence":"additional","affiliation":[{"name":"General Directorate of Scientific Research Center, Salahaddin University-Erbil, Erbil 44001, Iraq"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9201-0991","authenticated-orcid":false,"given":"Dara K.","family":"Mohammad","sequence":"additional","affiliation":[{"name":"Center for Hematology and Regenerative Medicine (HERM), Department of Medicine Huddinge, Karolinska Institutet, SE-141 83 Stockholm, Sweden"},{"name":"College of Agricultural Engineering Sciences, Salahaddin University-Erbil, Erbil 44001, Iraq"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2735","DOI":"10.1073\/pnas.0811073106","article-title":"MicroRNA-155 modulates the interleukin-1 signaling pathway in activated human monocyte-derived dendritic cells","volume":"106","author":"Ceppi","year":"2009","journal-title":"Proc. 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