文章基本信息

标题：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
本地全文：下载
作者：Kim R. Simpfendorfer ; Wentian Li ; Andrew Shih 等
期刊名称：Molecular Genetics and Metabolism Reports
印刷版ISSN：2214-4269
出版年度：2019
卷号：19
页码：1-5
DOI：10.1016/j.ymgmr.2019.100470
出版社：Elsevier B.V.
摘要：Objectives 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. Methods 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. Results 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. Conclusions 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.
关键词：GLUT3 ; SLC2A3 ; Glycolysis ; Deletion ; Rheumatoid arthritis ; Copy number variant ; Glucose transport