title: Susceptibility to SLE in South Indian Tamils may be influenced by genetic selection pressure on TLR2 and TLR9 genes.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Immunology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry 605 006, India.
authors.forename: Panneer
authors.initials: P
authors.lastname: Devaraju
authors.affiliation: Genetic Services Unit, Department of Pediatrics, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry 605 006, India.
authors.forename: Reena
authors.initials: R
authors.lastname: Gulati
authors.affiliation: Department of Clinical Immunology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry 605 006, India.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Antony
authors.affiliation: Department of Clinical Immunology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry 605 006, India.
authors.forename: C B
authors.initials: CB
authors.lastname: Mithun
authors.affiliation: Department of Clinical Immunology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry 605 006, India. Electronic address: vsnegi22@yahoo.co.in.
authors.forename: Vir S
authors.initials: VS
authors.lastname: Negi
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000276:immunology; D016022:Case-Control Studies; D003710:Demography; D005260:Female; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012641:Selection, Genetic; D051195:Toll-Like Receptor 2 / Q000235:genetics*; D051217:Toll-Like Receptor 9 / Q000235:genetics*
chemical_list: D001323:Autoantibodies; C495342:TLR2 protein, human; C495371:TLR9 protein, human; D051195:Toll-Like Receptor 2; D051217:Toll-Like Receptor 9
keywords: Autoantibodies; Polymorphism; SLE; Selection pressure; TLR