title: Association of single nucleotide polymorphisms in the gene encoding GLUT1 and diabetic nephropathy in Brazilian patients with type 1 diabetes mellitus.
abstract: 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 ± 2.4 years 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.
authors.affiliation: Laboratório de Endocrinologia Celular e Molecular (LIM-25), Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo, 455 #4305, 01246-903 São Paulo-SP, Brazil.
authors.forename: T
authors.initials: T
authors.lastname: Marques
authors.affiliation: Laboratório de Endocrinologia Celular e Molecular (LIM-25), Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo, 455 #4305, 01246-903 São Paulo-SP, Brazil.
authors.forename: T A
authors.initials: TA
authors.lastname: Patente
authors.affiliation: Laboratório de Endocrinologia Celular e Molecular (LIM-25), Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo, 455 #4305, 01246-903 São Paulo-SP, Brazil.
authors.forename: M B
authors.initials: MB
authors.lastname: Monteiro
authors.affiliation: Laboratório de Endocrinologia Celular e Molecular (LIM-25), Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo, 455 #4305, 01246-903 São Paulo-SP, Brazil.
authors.forename: A M
authors.initials: AM
authors.lastname: Cavaleiro
authors.affiliation: Divisão de Endocrinologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, R. Dr. Eneas de Carvalho Aguiar, 647, 05403-000 São Paulo-SP, Brazil.
authors.forename: M S
authors.initials: MS
authors.lastname: Queiroz
authors.affiliation: Divisão de Endocrinologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, R. Dr. Eneas de Carvalho Aguiar, 647, 05403-000 São Paulo-SP, Brazil.
authors.forename: M
authors.initials: M
authors.lastname: Nery
authors.affiliation: Divisão de Endocrinologia, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, R. Ramiro Barcelos, 2350, 90035-903 Porto Alegre-RS, Brazil.
authors.forename: M J
authors.initials: MJ
authors.lastname: de Azevedo
authors.affiliation: Divisão de Endocrinologia, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, R. Ramiro Barcelos, 2350, 90035-903 Porto Alegre-RS, Brazil.
authors.forename: L H
authors.initials: LH
authors.lastname: Canani
authors.affiliation: Divisão de Endocrinologia, Departamento de Clínica Médica, Faculdade de Medicina da Universidade Estadual de Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126, 13084-971 Campinas-SP, Brazil.
authors.forename: M C
authors.initials: MC
authors.lastname: Parisi
authors.affiliation: Divisão de Endocrinologia, Departamento de Clínica Médica, Faculdade de Medicina da Universidade Estadual de Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126, 13084-971 Campinas-SP, Brazil.
authors.forename: A
authors.initials: A
authors.lastname: Moura-Neto
authors.affiliation: Laboratório de Lípides (LIM-10), Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo, 455 # 3305, 01246-903 São Paulo-SP, Brazil.
authors.forename: M
authors.initials: M
authors.lastname: Passarelli
authors.affiliation: Programa de Pós-Graduação em Medicina, Universidade Nove de Julho-UNINOVE, São Paulo-SP, Brazil.
authors.forename: D
authors.initials: D
authors.lastname: Giannella-Neto
authors.affiliation: Departmento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas da Universidade de São Paulo, Av. Prof. Lineu Prestes 1524, 05508-900 São Paulo-SP, Brazil.
authors.forename: U F
authors.initials: UF
authors.lastname: Machado
authors.affiliation: Laboratório de Endocrinologia Celular e Molecular (LIM-25), Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo, 455 #4305, 01246-903 São Paulo-SP, Brazil; Centro de Terapia Celular e Molecular (NUCEL/NETCEM) da FMUSP, São Paulo, Brazil.
authors.forename: M L
authors.initials: ML
authors.lastname: Corrêa-Giannella
mesh_terms: D000328:Adult; D001938:Brazil; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D003929:Diabetic Neuropathies / Q000235:genetics*; D005260:Female; D005838:Genotype; D051272:Glucose Transporter Type 1 / Q000235:genetics*; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D051272:Glucose Transporter Type 1; C495677:SLC2A1 protein, human
keywords: Diabetic nephropathy; Genetic susceptibility; Glucose transporter-1