{Reference Type}: Journal Article
{Title}: Influence of genetic copy number variants of the human GLUT3 glucose transporter gene SLC2A3 on protein expression, glycolysis and rheumatoid arthritis risk: A genetic replication study.
{Author}: Simpfendorfer KR;Li W;Shih A;Wen H;Kothari HP;Einsidler EA;Wuster A;Hunkapiller J;Behrens TW;Graham RR;Townsend MJ;Behar DM;Hu R;Greenspan E;Gregersen PK;
{Journal}: Mol Genet Metab Rep
{Volume}: 19
{Issue}: 0
{Year}: Jun 2019
{Factor}: 2.082
{DOI}: 10.1016/j.ymgmr.2019.100470
{Abstract}: UNASSIGNED: The gene encoding glucose transporter 3 (GLUT3, SLC2A3) is present in the human population at variable copy number. An overt disease phenotype of SLC2A3 copy number variants has not been reported; however, deletion of SLC2A3 has been previously reported to protect carriers from rheumatoid arthritis, implicating GLUT3 as a therapeutic target in rheumatoid arthritis. Here we aim to perform functional analysis of GLUT3 copy number variants in immune cells, and test the reported protective association of the GLUT3 copy number variants for rheumatoid arthritis in a genetic replication study.
UNASSIGNED: Cells from genotyped healthy controls were analyzed for SLC2A3/GLUT3 expression and glycolysis capacity. We genotyped the SLC2A3 copy number variant in four independent cohorts of rheumatoid arthritis and controls and one cohort of multiple sclerosis and controls.
UNASSIGNED: Heterozygous deletion of SLC2A3 correlates directly with expression levels of GLUT3 and influences glycolysis rates in the human immune system. The frequency of the SLC2A3 copy number variant is not different between rheumatoid arthritis, multiple sclerosis and control groups.
UNASSIGNED: Despite a robust SLC2A3 gene copy number dependent phenotype, our study of large groups of rheumatoid arthritis cases and controls provides no evidence for rheumatoid arthritis disease protection in deletion carriers. These data emphasize the importance of well powered replication studies to confirm or refute genetic associations, particularly for relatively rare variants.