PhD Scientific Days 2022

Budapest, 6-7 July 2022

Molecular Sciences II.

Genetic modulators of the expression of GLUT1 (SLC2A1) transporter protein - potential relevance in complex diseases

Anna Kulin1,2, Botond Literáti-Nagy3, László Korányi3, Judit Cserepes4, Anikó Somogyi5, Balázs Sarkadi1.6, Edit Szabó1 and György Várady1
1 Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary
2 Semmelweis University, Doctoral School of Molecular Medicine, Budapest, Hungary
3 Drug Research Center, Balatonfüred, Hungary
4 CellPharma Kft, Budapest, Hungary
5 Semmelweis University, 2nd Department of Internal Medicine, Budapest, Hungary
6 Semmelweis University, Department of Biophysics and Radiation Biology, Budapest, Hungary

Text of the abstract

Introduction: The human GLUT1 (SLC2A1) membrane protein is the key glucose transporter in numerous cell types, including red cells, kidney mesangial cells and endothelial cells of the blood brain barrier. Alterations in the expression levels of this protein play a role in many diseases, such as cancer, COPD, or Alzheimer's disease.
Aim: In this work, we have investigated the genetic factors modulating the level of the GLUT1 protein.
Methods: The expression level of GLUT1 was measured in red cell membranes by flow cytometry and the genetic background was analyzed in genomic DNA samples, by sequencing and qPCR. To explore the GLUT1 expression modulating effects of the genetic background, the relevant SNPs were further studied by using luciferase reporter expression in HEK293T and HepG2 hepatoma cell models.
Results: We found significant associations between red cell membrane GLUT1 protein levels and four single nucleotide polymorphisms (SNPs) in SLC2A1. Individuals carrying the minor SNP alleles of rs841848, rs1385129 and rs11537641 had increased, while those carrying the rs841847 SNP had decreased GLUT1 expression levels. In cellular assays a similar SNP-dependent modulation of the reporter expression was observed as found for GLUT1 in the red cell membranes. Moreover, low concentrations of glucose had variable, SNP-specific effects on cellular reporter expression.
Conclusion: These results should contribute to a more detailed understanding of the genetic background of GLUT1 protein expression and its potential role in associated diseases.
Funding:

EFOP-3.6.3-VEKOP-16-2017-00009, Semmelweis University, Development of scientific workshops of medical, health sciences and pharmaceutical educations;
NKFIH OTKA (K128011)