Genetic Variants of the Human Thiamine Transporter (SLC19A3, THTR2)—Potential Relevance in Metabolic Diseases

Thiamine, crucial for energy metabolism, is associated with various human diseases when deficient. We studied how variations in the <i>SLC19A3</i> gene, encoding THTR2, a thiamine transporter, may influence type 2 diabetes (T2DM) and gout (arthritis urica, AU). We characterized the <i>SLC19A3</i> 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 (H1-4) 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 (<i>p</i> = 0.0008) and white blood cell levels (<i>p</i> = 0.0272). In AU patients, H3-MV correlated with increased basophil granulocyte levels (<i>p</i> = 0.0273). In model cell lines, H3-MV presence increased gene expression (<i>p</i> = 0.0351), influencing responses to thiamine depletion and metformin (<i>p</i> = 0.0016). Although H4-MV did not directly affect luciferase expression, thiamine and fedratinib co-treatment significantly enhanced gene expression in thiamine-depleted cells (<i>p</i> = 0.04854). Our results suggest a connection between selected <i>SLC19A3</i> variants and the severity of metabolic diseases or their response to treatment.