XbaI GLUT1 Gene Polymorphism and the Risk of Type 2 Diabetes with Nephropathy

Abstract

Altered expression of the facilitated glucose transporter GLUT1 affects pathways implicated in the pathogenesis of diabetic nephropathy. There is indication that variation of GLUT1 gene (SLC2A1) contributes to development of microangiopathy in diabetes mellitus type 2 (DM) patients. A genetic association study involving Caucasians was carried out to investigate the role of XbαI polymorphism in the GLUT1 gene in diabetic nephropathy (DN). Study population (n = 240) consisted of 148 unrelated patients with DM (92 cases with diabetic nephropathy (DN)), and of 92 matched healthy control subjects. Diabetic nephropathy was defined as persistent albuminuria (> 300 mg/24 h) and/or renal failure, in the absence of non-diabetes induced renal disease. The analysis showed that the risk of developing DM and DN in XbaI(−) carriers, when healthy individuals were considered as controls, was two-fold: odds ratio (OR) 2.08 [95% confidence interval (1.14–3.79)]. However, there was no evidence of association between XbaI(−) and DN when patients with DM and without DN were considered as controls: OR = 1.12 (0.55–2.26). Thus, the GLUT1 XbaI(−) allele is associated with DM, and possibly with a more severe form of the disease that can lead to development of DN.

Association of XbaI <i>GLUT</i>1 Polymorphism with Susceptibility to Type 2 Diabetes Mellitus and Diabetic Nephropathy

“…GLUT1 gene (SLC2A1) (rs841853) is located on chromosome 1p34.2, and it contains 10 exons and 9 introns [6] [7]. It has a central role in the pathogenesis of DN because over expression of GLUT-1 in glomerular mesangial cells is expected to augment the basal glucose uptake [8], and activate cellular pathways involved in cellular growth and in accumulation of the extracellular matrix [9]. The expression and activity of mesangial GLUT1 in diabetic patients comprise great individual variability attributed mostly to genetic causes.…”

“…Thus investigating the genetic susceptibility to the development of DN may shed light on the pathogenesis of renal involvement in diabetes mellitus. Several single nucleotide polymorphisms (SNP) of GLUT1 gene have been examined in relation to DN, of which is XbaI G > T, located within intron 2, which represents transversion of guanine (G) to thymine (T) [9].…”

“…The conflicting data from worldwide studies done concerning XbaI G > T GLUT1 polymorphism in relation to DN [1] [9], and the fact that there were no studies in Egyptian population concerning this issue, made it noteworthy to study this polymorphism.…”

Roles of facilitative glucose transporter GLUT1 in [18F]FDG positron emission tomography (PET) imaging of human diseases

“…Glucose transport in the diabetic kidney is upregulated and has been implicated in the pathogenesis of progressive diabetic nephropathy [372]. Hyperglycemia, hypertension and activation of the reninangiotensin system are thought to be important in the development of the disease and expression levels of GLUT1 are elevated under conditions of hypertension and diabetic nephropathy [373,374].…”

“…Polymorphisms of the GLUT1 gene are associated with susceptibility to diabetic nephropathy in both type 1 and type 2 diabetes [372,[375][376][377]. Skeletal muscle GLUT1 expression and basal leg glucose uptake are reduced in type 2 diabetes [378].…”