Toll-like receptor-4 (TLR4) is a primary receptor of the innate immune reaction and compelling evidence demonstrates itsinvolvement in the pathogenesis of atherosclerosis and stroke. TLR4 is constitutively expressed on monocytes and endothelialcells; it is highly expressed in atherosclerotic plaques and in peripheral blood of patients after ischemic stroke. Polymorphismsin the promoter region that alter the transcriptional regulation of this gene may represent genetic risk factors involved in thepredisposition to atherosclerotic disease. In this study we investigated the effect on TLR4 gene expression of threepolymorphisms in the upstream regulatory region at positions 1607T4C/rs10759932, 2026A4G/rs1927914 and2604G4A/rs10759931 in peripheral blood of atherosclerotic patients. RNA from individuals homozygous for the 2604Aallele showed a lower expression of the gene when compared to patients carrying the counterparts GGþGA. Electrophoreticmobility shift assays showed differences in the electrophoretic mobility of the DNA–nuclear protein complexes formed by theG4A variants, suggesting that the two alleles differ in their binding affinity to transcriptional factors.

Polymorphism -2604G>A variants in TLR4 promoter are associated with different gene expression level in peripheral blood of atherosclerotic patients.

FERRONATO, Silvia;GOMEZ, Maria Macarena;MENEGAZZI, Marta Vittoria;DIANI, ERICA;OLIVATO, Silvia;SCURO, Alberto;MALERBA, Giovanni;PIGNATTI, Pierfranco;ROMANELLI, Maria;MAZZUCCO, Sara
2013

Abstract

Toll-like receptor-4 (TLR4) is a primary receptor of the innate immune reaction and compelling evidence demonstrates itsinvolvement in the pathogenesis of atherosclerosis and stroke. TLR4 is constitutively expressed on monocytes and endothelialcells; it is highly expressed in atherosclerotic plaques and in peripheral blood of patients after ischemic stroke. Polymorphismsin the promoter region that alter the transcriptional regulation of this gene may represent genetic risk factors involved in thepredisposition to atherosclerotic disease. In this study we investigated the effect on TLR4 gene expression of threepolymorphisms in the upstream regulatory region at positions 1607T4C/rs10759932, 2026A4G/rs1927914 and2604G4A/rs10759931 in peripheral blood of atherosclerotic patients. RNA from individuals homozygous for the 2604Aallele showed a lower expression of the gene when compared to patients carrying the counterparts GGþGA. Electrophoreticmobility shift assays showed differences in the electrophoretic mobility of the DNA–nuclear protein complexes formed by theG4A variants, suggesting that the two alleles differ in their binding affinity to transcriptional factors.
TLR4 gene expression; TLR4 polymorphisms; atherosclerosis; peripheral blood
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11562/625962
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