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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Linkage disequilibrium with HLA-DRB1-DQB1 haplotypes explains the association of TNF-308G > A variant with type 1 diabetes in a Brazilian cohort

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Autor(es):
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Patente, Thiago A. [1] ; Monteiro, Maria B. [1] ; Vieira, Suzana M. [2] ; Rossi da Silva, Maria E. [3, 4] ; Nery, Marcia [3] ; Queiroz, Marcia [3] ; Azevedo, Mirela J. [5] ; Canani, Luis H. [5] ; Parisi, Maria C. [6] ; Pavin, Elizabeth J. [6] ; Mainardi, Debora [4] ; Javor, Juraj [7] ; Velho, Gilberto [8] ; Coimbra, Cassio N. [9] ; Correa-Giannella, Maria Lucia [1, 10]
Número total de Autores: 15
Afiliação do(s) autor(es):
[1] Univ Sao Paulo FMUSP, Fac Med, Lab Endocrinol Celular & Mol LIM 25, Sao Paulo - Brazil
[2] HSPE, Sao Paulo - Brazil
[3] FMUSP, Hosp Clin, Div Endocrinol, Sao Paulo - Brazil
[4] FMUSP, Lab Invest Med LIM 18, Sao Paulo - Brazil
[5] Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Div Endocrinol, BR-90046900 Porto Alegre, RS - Brazil
[6] Univ Estadual Campinas UNICAMP, Fac Med, Dept Clin Med, Div Endocrinol, Sao Paulo - Brazil
[7] Comenius Univ, Fac Med, Dept Immunol, Bratislava - Slovakia
[8] INSERM, Res Unit 1138, Equipe 2, Paris - France
[9] Univ Santo Amaro UNISA, Sao Paulo - Brazil
[10] FMUSP, Ctr Terapia Celular & Mol NUCEL NETCEM, Sao Paulo - Brazil
Número total de Afiliações: 10
Tipo de documento: Artigo Científico
Fonte: Gene; v. 568, n. 1, p. 50-54, AUG 15 2015.
Citações Web of Science: 5
Resumo

Background: A functional variant in the promoter region of the gene encoding tumor necrosis factor (TNF; rs1800629, -308G>A) showed to confer susceptibility to T1D. However, TNF rs1800629 was found, in several populations, to be in linkage disequilibrium with HLA susceptibility haplotypes to T1D. We evaluated the association of TNF rs1800629 with T1D in a cohort of Brazilian subjects, and assessed the impact of HLA susceptibility haplotypes in this association.. Methods: 659 subjects with T1D and 539 control subjects were genotyped for TNF-308G>A variant. HLA-DRB1 and HIA-DQB1 genes were genotyped in a subset of 313 subjects with T1D and 139 control subjects. Results: Associations with T1D were observed for the A-allele of rs1800629 (OR 1.69,95% Cl 133-2.15, p < 0.0001, in a codominant model) and for 3 HLA haplotypes: DRB1{*}03:01-DQB1{*}02:01 (OR 5.37, 95% Cl 3.23-8.59, p < 0.0001), DRB1{*}04:01-DQB1{*}03:02 (OR 2.95, 95% Cl 1.21-7.21, p = 0.01) and DRB1{*}04:02-DQB1{*}03:02 (OR 2.14,95% Cl 1.02-4.50, p = 0.04). Linkage disequilibrium was observed between TNF rs1800629 and HLA-DRB1 and HLA-DQB1 alleles. In a stepwise regression analysis HLA haplotypes, but not TNF rs1800629, remained independently associated with T1D. Conclusion: Our results do not support an independent effect of allelic variations of TNF in the genetic susceptibility to T1D. (C) 2015 Elsevier B.V. All rights reserved. (AU)

Processo FAPESP: 10/04305-2 - Avaliação do polimorfismo G-308A na região promotora do gene do fator de necrose tumoral - alfa e sua associação com o desenvolvimento de nefropatia em pacientes diabéticos tipo 1.
Beneficiário:Thiago Andrade Patente
Modalidade de apoio: Bolsas no Brasil - Iniciação Científica