Association of single nucleotide polymorphisms in the gene encoding GLUT1 and diabetic nephropathy in Brazilian patients with type 1 diabetes mellitus

• Published in: Clinica chimica acta Vol. 444; pp. 170 - 175
• Main Authors: Marques, T., Patente, T.A., Monteiro, M.B., Cavaleiro, A.M., Queiroz, M.S., Nery, M., de Azevedo, M.J., Canani, L.H., Parisi, M.C., Moura-Neto, A., Passarelli, M., Giannella-Neto, D., Machado, U.F., Corrêa-Giannella, M.L.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.04.2015
• Subjects: Adult; Brazil; Cross-Sectional Studies; Diabetes Mellitus, Type 1 - genetics; Diabetic nephropathy; Diabetic Neuropathies - genetics; Female; Genetic susceptibility; Genotype; Glucose Transporter Type 1 - genetics; Glucose transporter-1; Humans; Male; Polymorphism, Single Nucleotide - genetics; Brazil; Genetic susceptibility; Glucose transporter-1; Diabetic nephropathy
• ISSN: 0009-8981; 1873-3492; 1873-3492
• DOI: 10.1016/j.cca.2015.02.025

Mesangial cells subject to high extracellular glucose concentrations, as occur in hyperglycaemic states, are unable to down regulate glucose influx, resulting in intracellular activation of deleterious biochemical pathways. A high expression of GLUT1 participates in the development of diabetic glomerulopathy. Variants in the gene encoding GLUT1 (SLC2A1) have been associated to this diabetic complication. The aim of this study was to test whether polymorphisms in SLC2A1 confer susceptibility to diabetic nephropathy (DN) in Brazilian type 1 diabetes patients. Four polymorphisms (rs3820589, rs1385129, rs841847 and rs841848) were genotyped in a Brazilian cohort comprised of 452 patients. A prospective analysis was performed in 155 patients. Mean duration of follow-up was 5.6±2.4years and the incidence of renal events was 18.0%. The rs3820589 presented an inverse association with the prevalence of incipient DN (OR: 0.36, 95% CI: 0.16 – 0.80, p=0.01) and with progression to renal events (HR: 0.20; 95% CI: 0.03 – 0.70; p=0.009). AGGT and AGAC haplotypes were associated with the prevalence of incipient DN and the AGAC haplotype was also associated with the prevalence of established/advanced DN. In conclusion, rs3820589 in the SLC2A1 gene modulates the risk to DN in Brazilian patients with inadequate type 1 diabetes control. •We studied four polymorphisms in the SLC2A1 gene in a type 1 diabetic cohort.•We observe an association of the rs3820589 with the prevalence of incipient diabetic nephropathy.•We report an association of the rs3820589 with the incidence of renal events.