{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T18:36:59Z","timestamp":1770748619995,"version":"3.50.0"},"reference-count":45,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T00:00:00Z","timestamp":1742860800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hungarian National Development and Innovation Office","award":["NKFIH K-128011"],"award-info":[{"award-number":["NKFIH K-128011"]}]},{"name":"Hungarian National Development and Innovation Office","award":["MRE-KP-24-1-I"],"award-info":[{"award-number":["MRE-KP-24-1-I"]}]},{"name":"Research Grant-2024 from The Hungarian Association of Rheumatologists","award":["NKFIH K-128011"],"award-info":[{"award-number":["NKFIH K-128011"]}]},{"name":"Research Grant-2024 from The Hungarian Association of Rheumatologists","award":["MRE-KP-24-1-I"],"award-info":[{"award-number":["MRE-KP-24-1-I"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Thiamine, crucial for energy metabolism, is associated with various human diseases when deficient. We studied how variations in the SLC19A3 gene, encoding THTR2, a thiamine transporter, may influence type 2 diabetes (T2DM) and gout (arthritis urica, AU). We characterized the SLC19A3 gene variants using bioinformatics and analyzed DNA samples from controls, T2DM, and gout patients to explore associations with physical\/laboratory parameters. In human cells, we used a luciferase reporter assay to assess how these variants affect gene expression. We examined four large haplotypes (H1\u20134) in this gene, identified lead SNPs for the minor variants (MV), and explored potential transcription factor binding sites. We found that in T2DM patients, H3-MV correlated significantly with impaired glucose metabolism (pHOMA = 0.0189, pHbA1c% = 0.0102), while H4-MV correlated with altered uric acid (p = 0.0008) and white blood cell levels (p = 0.0272). In AU patients, H3-MV correlated with increased basophil granulocyte levels (p = 0.0273). In model cell lines, H3-MV presence increased gene expression (p = 0.0351), influencing responses to thiamine depletion and metformin (p = 0.0016). Although H4-MV did not directly affect luciferase expression, thiamine and fedratinib co-treatment significantly enhanced gene expression in thiamine-depleted cells (p = 0.04854). Our results suggest a connection between selected SLC19A3 variants and the severity of metabolic diseases or their response to treatment.<\/jats:p>","DOI":"10.3390\/ijms26072972","type":"journal-article","created":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T06:25:15Z","timestamp":1742883915000},"page":"2972","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Genetic Variants of the Human Thiamine Transporter (SLC19A3, THTR2)\u2014Potential Relevance in Metabolic Diseases"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0150-0926","authenticated-orcid":false,"given":"Edit","family":"Szab\u00f3","sequence":"first","affiliation":[{"name":"Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, 1117 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00e1rton","family":"P\u00e1link\u00e1s","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Semmelweis University, 1023 Budapest, Hungary"},{"name":"Department of Internal Medicine and Haematology, Semmelweis University, 1088 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bal\u00e1zs","family":"Boh\u00e1r","sequence":"additional","affiliation":[{"name":"Doctoral School of Biology, E\u00f6tv\u00f6s Lor\u00e1nd University, 1117 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1319-6474","authenticated-orcid":false,"given":"Botond","family":"Liter\u00e1ti-Nagy","sequence":"additional","affiliation":[{"name":"Drug Research Center, 8230 Balatonf\u00fcred, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L\u00e1szl\u00f3","family":"Kor\u00e1nyi","sequence":"additional","affiliation":[{"name":"Drug Research Center, 8230 Balatonf\u00fcred, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gyula","family":"Po\u00f3r","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Semmelweis University, 1023 Budapest, Hungary"},{"name":"Department of Internal Medicine and Haematology, Semmelweis University, 1088 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2012-9680","authenticated-orcid":false,"given":"Gy\u00f6rgy","family":"V\u00e1rady","sequence":"additional","affiliation":[{"name":"Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, 1117 Budapest, Hungary"},{"name":"Doctoral School, Semmelweis University, 1085 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0592-4539","authenticated-orcid":false,"given":"Bal\u00e1zs","family":"Sarkadi","sequence":"additional","affiliation":[{"name":"Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, 1117 Budapest, Hungary"},{"name":"Doctoral School, Semmelweis University, 1085 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/S1474-4422(07)70104-7","article-title":"Wernicke\u2019s Encephalopathy: New Clinical Settings and Recent Advances in Diagnosis and Management","volume":"6","author":"Sechi","year":"2007","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1556\/OH.2014.29847","article-title":"Wernicke\u2019s Encephalopathy Induced by the Use of Diet Pills and Unbalanced Diet","volume":"155","author":"Aradi","year":"2014","journal-title":"Orv. 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