Genetic Variants of the Human Thiamine Transporter (, 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 gene, encoding THTR2, a thiamine transporter, may influence type 2 diabetes (T2DM) and gout (arthritis urica, AU). We characterized the 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 ( = 0.0008) and white blood cell levels ( = 0.0272). In AU patients, H3-MV correlated with increased basophil granulocyte levels ( = 0.0273). In model cell lines, H3-MV presence increased gene expression ( = 0.0351), influencing responses to thiamine depletion and metformin ( = 0.0016). Although H4-MV did not directly affect luciferase expression, thiamine and fedratinib co-treatment significantly enhanced gene expression in thiamine-depleted cells ( = 0.04854). Our results suggest a connection between selected variants and the severity of metabolic diseases or their response to treatment.