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

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.