Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/354126
Type: Artigo
Title: Linkage disequilibrium with HLA-DRB1-DQB1 haplotypes explains the association of TNF-308G > a variant with Type 1 Diabetes in a brazilian cohort
Author: Patente, Thiago A.
Monteiro, Maria B.
Vieira, Suzana M.
Rossi da Silva, Maria E.
Nery, Marcia
Queiroz, Marcia
Azevedo, Mirela J.
Canani, Luis H.
Parisi, Maria C.
Pavin, Elizabeth J.
Mainardi, Debora
Javor, Juraj
Velho, Gilberto
Coimbra, Cassio N.
Correa-Giannella, Maria Lucia
Abstract: 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. 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. 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. Our results do not support an independent effect of allelic variations of TNF in the genetic susceptibility to T1D
Subject: Polimorfismo de nucleotídeo único
Diabetes Mellitus tipo 1A
Country: Países Baixos
Editor: Elsevier
Rights: Fechado
Identifier DOI: 10.1016/j.gene.2015.05.017
Address: https://www.sciencedirect.com/science/article/pii/S0378111915005752
Date Issue: 2015
Appears in Collections:FCM - Artigos e Outros Documentos

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