D09 Thiamine and Energy Metabolism Related Genes Profiling in Lymphocytes B of Healthy Control and HD Patient - Search of Biomarkers

Abstract

The cause of the energy deficits in HD pathogenesis is unknown but impaired glycolysis or TCA cycle may be involved. Subcellular abnormalities were observed among others also in peripheral tissues of HD patients. Thiamine–dependent enzymes are diminished in multiple neurodegenerative diseases. Deficit of that vitamin evokes not only reduction in thiamine dependent enzymes but also in the other TCA enzymes. The aim of the study was to follow the effects of thiamine supplementation on the profiles of the thiamine linked genes as well as the genes involved in Krebs cycle in B-lymphocytes of patients with HD (GM13509) compared to the cells of healthy individuals (GM14467) with use of qPCR. The intact GM13509 cells differed from GM14467 cells in the higher expression of: MDH1, GAPDH and SLC19A3 genes. The expression of DLD, IDH1, SDHA and SLC19A1 decreased in GM13509 cells upon thiamine deficit or low thiamine level. The genes: DBT, DLST, ACO1, OGDH, SLC19A2, SLC25A19 and DLAT in GM13509 cells showed lower level of mRNA than the GM14467 cells under thiamine supplemented. The inverse correlation was observed between thiamine levels and GAPDH and SLC25A3 expression. The analysis of the genes in the intact B-lymphocytes showed that energy may characterise HD, but the thiamine related genes did not seem to be a key point in the gene profiles. However, the 2-fold decrease in the IDH1 gene expression in GM13509 cells which was noted upon thiamine deficit suggests that low thiamine intracellular level somehow could be reflected in energy metabolism of HD peripheral tissues.