Type I diabetes mellitus (T1DM) is an autoimmune disorder featured by raised glucoses levels. It hasbeen hypothesised that raised glucose levels in T1DM might be recognised as PAMPs, leading to immuneresponse by overloading the cell receptors for pathogens recognition. DC-SIGN is a transmembrane pro-tein, present in dendritic cells (DC) and macrophages: it has an important role in inflammatory responseand T cells activation. Notably, DC-SIGN activation and triggering of the immune response depend onthe type of ligand, which may lead to a pro or anti-inflammatory pathway. In our association study, weanalysed the SNPs rs4804803 (−336 A>G) and rs735239 (−871 A>G), both at DC-SIGN promoter region,in 210 T1DM patients and 157 healthy controls, also looking for a correlation with the age of onset ofthe disease. We found that the allele G and genotypes G/G and A/G of SNP-871 (rs735239), as well as thealleles G-G (rs735239-rs4804803) and genotypes combined AA-GG (rs735239-rs4804803) were associ-ated with protection of T1DM development. We did not find association between these variations withthe age of onset of the disease and the presence of other autoimmune disorders. Our results suggest thatSNPs in DC-SIGN promoter region can be associated to protection for T1DM in the Northeast Brazilianpopulation.

DC-SIGN polymorphisms are associated to type 1 diabetes mellitus

CROVELLA, SERGIO;
2014-01-01

Abstract

Type I diabetes mellitus (T1DM) is an autoimmune disorder featured by raised glucoses levels. It hasbeen hypothesised that raised glucose levels in T1DM might be recognised as PAMPs, leading to immuneresponse by overloading the cell receptors for pathogens recognition. DC-SIGN is a transmembrane pro-tein, present in dendritic cells (DC) and macrophages: it has an important role in inflammatory responseand T cells activation. Notably, DC-SIGN activation and triggering of the immune response depend onthe type of ligand, which may lead to a pro or anti-inflammatory pathway. In our association study, weanalysed the SNPs rs4804803 (−336 A>G) and rs735239 (−871 A>G), both at DC-SIGN promoter region,in 210 T1DM patients and 157 healthy controls, also looking for a correlation with the age of onset ofthe disease. We found that the allele G and genotypes G/G and A/G of SNP-871 (rs735239), as well as thealleles G-G (rs735239-rs4804803) and genotypes combined AA-GG (rs735239-rs4804803) were associ-ated with protection of T1DM development. We did not find association between these variations withthe age of onset of the disease and the presence of other autoimmune disorders. Our results suggest thatSNPs in DC-SIGN promoter region can be associated to protection for T1DM in the Northeast Brazilianpopulation.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11368/2800732
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