PhD Scientific Days 2023

Molecular Sciences II.

Genetic and regulatory background of the GLUT1 transporter expression – Potential relevance in complex diseases

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 and regulatory 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 by sequencing and qPCR. The 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. As a potential regulatory factor, low concentrations of glucose had variable, SNP-specific effects on cellular reporter expression. Moreover, we found several transcription factor binding sites related to the variants.
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;
NKFIH OTKA (K128011)