{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T08:56:45Z","timestamp":1765357005234,"version":"build-2065373602"},"reference-count":103,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2021,9,18]],"date-time":"2021-09-18T00:00:00Z","timestamp":1631923200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012155","name":"National Institute for Medical Research Development","doi-asserted-by":"publisher","award":["958382"],"award-info":[{"award-number":["958382"]}],"id":[{"id":"10.13039\/501100012155","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hashimoto thyroiditis (HT) is a common autoimmune disorder with a strong genetic background. Several genetic factors have been suggested, yet numerous genetic contributors remain to be fully understood in HT pathogenesis. MicroRNAs (miRs) are gene expression regulators critically involved in biological processes, of which polymorphisms can alter their function, leading to pathologic conditions, including autoimmune diseases. We examined whether miR-499 rs3746444 polymorphism is associated with susceptibility to HT in an Iranian subpopulation. Furthermore, we investigated the potential interacting regulatory network of the miR-499. This case-control study included 150 HT patients and 152 healthy subjects. Genotyping of rs3746444 was performed by the PCR-RFLP method. Also, target genomic sites of the polymorphism were predicted using bioinformatics. Our results showed that miR-499 rs3746444 was positively associated with HT risk in heterozygous (OR = 3.32, 95%CI = 2.00\u20135.53, p &lt; 0.001, CT vs. TT), homozygous (OR = 2.81, 95%CI = 1.30\u20136.10, p = 0.014, CC vs. TT), dominant (OR = 3.22, 95%CI = 1.97\u20135.25, p &lt; 0.001, CT + CC vs. TT), overdominant (OR = 2.57, 95%CI = 1.62\u20134.09, p &lt; 0.001, CC + TT vs. CT), and allelic (OR = 1.92, 95%CI = 1.37\u20132.69, p &lt; 0.001, C vs. T) models. Mapping predicted target genes of miR-499 on tissue-specific-, co-expression-, and miR-TF networks indicated that main hub-driver nodes are implicated in regulating immune system functions, including immunorecognition and complement activity. We demonstrated that miR-499 rs3746444 is linked to HT susceptibility in our population. However, predicted regulatory networks revealed that this polymorphism is contributing to the regulation of immune system pathways.<\/jats:p>","DOI":"10.3390\/ijms221810094","type":"journal-article","created":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T08:04:23Z","timestamp":1632211463000},"page":"10094","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Association of miR-499 Polymorphism and Its Regulatory Networks with Hashimoto Thyroiditis Susceptibility: A Population-Based Case-Control Study"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4877-0701","authenticated-orcid":false,"given":"Farhad","family":"Tabasi","sequence":"first","affiliation":[{"name":"Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan 9816743463, Iran"},{"name":"Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran 1411713116, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vahed","family":"Hasanpour","sequence":"additional","affiliation":[{"name":"Student Research Committee, School of Medicine, Zahedan University of Medical Sciences, Zahedan 9816743463, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shamim","family":"Sarhadi","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz 5166616471, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2994-4243","authenticated-orcid":false,"given":"Mahmoud Ali","family":"Kaykhaei","sequence":"additional","affiliation":[{"name":"Genetics of Non-Communicable Disease Research Center, Zahedan University of Medical Sciences, Zahedan 9816743463, Iran"},{"name":"Department of Endocrinology, School of Medicine, Zahedan University of Medical Sciences, Zahedan 9816743463, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pouria","family":"Pourzand","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan 9816743463, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mehrdad","family":"Heravi","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan 9816743463, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3177-9489","authenticated-orcid":false,"given":"Ahmad Alinaghi","family":"Langari","sequence":"additional","affiliation":[{"name":"Student Research Committee, School of Medicine, Kerman University of Medical Sciences, Kerman 7616913555, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gholamreza","family":"Bahari","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan 9816743463, Iran"},{"name":"Children and Adolescent Health Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan 9816743463, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohsen","family":"Taheri","sequence":"additional","affiliation":[{"name":"Genetics of Non-Communicable Disease Research Center, Zahedan University of Medical Sciences, Zahedan 9816743463, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6074-7101","authenticated-orcid":false,"given":"Mohammad","family":"Hashemi","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan 9816743463, Iran"},{"name":"Genetics of Non-Communicable Disease Research Center, Zahedan University of Medical Sciences, Zahedan 9816743463, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5948-508X","authenticated-orcid":false,"given":"Saeid","family":"Ghavami","sequence":"additional","affiliation":[{"name":"Research Institute of Oncology and Hematology, Cancer Care Manitoba, University of Manitoba, Winnipeg, MB R3E 0V9, Canada"},{"name":"Biology of Breathing Theme, Children Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB R3E 0V9, Canada"},{"name":"Faculty of Medicine, Katowice School of Technology, 40-555 Katowice, Poland"},{"name":"Department of Human Anatomy and Cell Science, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1159\/000452541","article-title":"Imbalance of Th17\/treg in different subtypes of autoimmune thyroid diseases","volume":"40","author":"Li","year":"2016","journal-title":"Cell. 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