Susceptibility to SLE in South Indian Tamils may be influenced by genetic selection pressure on TLR2 and TLR9 genes

• Published in: Molecular immunology 2015-03, Vol.64 (1), p.123-126
• Main Authors: Devaraju, Panneer, Gulati, Reena, Antony, Paul T., Mithun, C.B., Negi, Vir S.
• Format: Article
• Language: English
• Subjects: Adult; Autoantibodies; Autoantibodies - immunology; Case-Control Studies; Demography; Female; Genetic Predisposition to Disease; Genotyping Techniques; Humans; Lupus Erythematosus, Systemic - genetics; Lupus Erythematosus, Systemic - immunology; Male; Phenotype; Polymorphism; Polymorphism, Single Nucleotide - genetics; Selection pressure; Selection, Genetic; SLE; TLR; Toll-Like Receptor 2 - genetics; Toll-Like Receptor 9 - genetics
• ISSN: 0161-5890; 1872-9142
• DOI: 10.1016/j.molimm.2014.11.005

•TLR2 gene remains monomorphic at position (G2408A) and failed to confer risk to develop SLE.•Whereas the TLR9 gene has adapted the mutation for its enhanced expression thereby conferred a significant risk to develop SLE.•Our findings suggests that the selection pressure exerted on these genes to combat the endemic infections turned out to be a genetic risk factor to develop autoimmune diseases like SLE. Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder with complex etiology. Genetics plays an important role in lupus pathogenesis through its influence on clinical and autoantibody phenotype of the disease. Toll like receptors (TLR) recognize molecular patterns of pathogens and activate the innate immune system. Their ability to identify nucleic acids makes them suitable candidates for investigation of their role in lupus pathogenesis. Hence, this study was carried out to analyze the G to A and C to T transitions in TLR2 and TLR9 genes respectively and to test their association with lupus susceptibility, clinical and autoantibody phenotypes in South Indian Tamils. Three hundred SLE patients fulfilling ACR 2012 criteria for SLE and 460 age, sex similar, ethnicity matched controls were recruited as cases and controls. TLR2 (R753Q) and TLR9 (−1237C/T) polymorphisms were analyzed by real time PCR. The TLR2 gene remained monomorphic in patients and controls, the frequency of the homozygous wild type allele being 100% and 99.6% respectively. Hence, it did not confer susceptibility to SLE. The more frequent T allele of TLR9 gene conferred a significant risk to develop SLE (p=0.011, OR 1.69, 95% CI 1.1–2.6). Both the polymorphisms did not influence clinical or autoantibody phenotype of the disease. Prevailing endemic infections in the Indian subcontinent may have exerted a selection pressure resulting in TLR2 gene remaining monomorphic and the TLR9 adapting to a mutation for its increased expression. These may have an additive effect in the presence of other genetic and environmental risk factors to confer susceptibility to SLE in South Indian Tamils.