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TIRAP (MAL) S180L polymorphism is a common protective factor against developing tuberculosis and systemic lupus erythematosus

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Castiblanco, John
Varela, Diana-Cristina
Castaño-Rodríguez, Natalia
Rojas-Villarraga, Adriana
Hincapié, María-Eugenia
Anaya, Juan-Manuel

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2008

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Abstract
Background and aim: The involvement of Toll-like receptor (TLR)-mediated pathways in infectious and autoimmunity has been suggested. The MyD88 adaptor-like (Mal) protein, also known as the TIR domain-containing adaptor protein (TIRAP), is implicated in the TLR2- and TLR4-mediated MyD88-dependent signaling pathway. The aim of this study was to investigate the influence of the functional TIRAP (MAL) S180L polymorphism on tuberculosis (TB) and four autoimmune diseases namely: rheumatoid arthritis (RA), primary Sjögren's syndrome (pSS), systemic lupus erythematosus (SLE) and type 1 diabetes mellitus (T1D). Methods: This was a case-control and family based association study in which 1325 individuals from a well-defined Colombian population were involved. TIRAP (MAL) S180L genotyping was done by using a polymerase chain reaction-restriction fragment length polymorphism technique and by direct sequencing. Results: Leu180 allele was found to be a protective factor against developing TB (odd ratio (OR): 0.53, 95% confidence interval (CI): 0.29-0.97) and SLE (OR: 0.29, 95% CI: 0.14-0.61) while no significant influence on RA, pSS and T1D was observed. Conclusion: These results support the influence of TIRAP (MAL) S180L polymorphism on TB and indicate that TB and SLE might share a common immunogenetic pathway in the innate immune response. © 2008 Elsevier B.V. All rights reserved.
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Adaptor protein , Leucine , systemic , interleukin-1 , genetic , Toll like receptor domain containing adaptor protein , Adult , Allele , Article , Autoimmune disease , Case control study , Colombia , Confidence interval , Controlled study , Family , Female , Gene sequence , Genetic polymorphism , Genetic susceptibility , Genotype , Human , Innate immunity , Insulin dependent diabetes mellitus , Major clinical study , Male , Polymerase chain reaction , Priority journal , Protection , Restriction fragment length polymorphism , Rheumatoid arthritis , Sjoegren syndrome , Systemic lupus erythematosus , Tuberculosis , Adult , Case-control studies , Colombia , Female , Gene frequency , Genotype , Humans , Lupus erythematosus , Male , Membrane glycoproteins , Middle aged , Polymorphism , Receptors , Tuberculosis , Mal , Rheumatoid arthritis , Sjögren's syndrome , Systemic lupus erythematosus , Tirap , Tuberculosis , Type 1 diabetes mellitus
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