title: Genetic variation of TLR-4, TLR-9 and TIRAP genes in Iranian malaria patients.
abstract: BACKGROUND
  Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns and their activation leads to the induction of effector genes involving inflammatory cytokines that may have contribute to controlling parasite growth and disease pathogenesis. The current immunogenetic study was designed to analyse the key components of innate immunity, TLRs and TIRAP (Toll-interleukin-1 receptor domain-containing adaptor protein), also known as MAL (MYD88 adaptor-like), in Iranian patients with mild malaria.
  
  
  METHODS
  The tlr-4 (D299G and T399I), tlr-9 (T-1486C and T-1237C) and tirap (S180L) genes were assessed in 640 Baluchi individuals (320 Plasmodium falciparum-infected and 320 non-infected, median age of 28 years) from malaria-endemic regions using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods.
  
  
  RESULTS
  Common tlr-4 SNPs and promoter SNPs of tlr-9 were distributed among P. falciparum-infected and non-infected groups (P > 0.05) that showed no association of these variants with mild clinical manifestation. The comparison of the tirap S180L genotypes between patients with mild malaria and those healthy individuals showed that the frequency of heterozygosity was significantly higher in infected than non-infected individuals (33.8 vs. 25.6; OR, 1.479; 95% CI, 1.051-2.081; P = 0.024). The result also revealed a significant association of tirap S180L (P < 0.05) with development of mild malaria, which is common in Baluchi populations, who are living in malaria hypoendemic region of Iran but not in African populations (0%-6%).
  
  
  CONCLUSIONS
  These data point towards the need for addressing the exact role of TLRs in contributing to human genetic factors in malaria susceptibility/resistance/severity within different malaria settings in the world.
authors: Malaria and Vector Research Group, Biotechnology Research Center, Institut Pasteur Iran, Tehran, Iran, Pasteur Avenue, POBOX 1316943551, Tehran, Iran. zakeris@yahoo.com
authors: Sedigheh
authors: S
authors: Zakeri
authors: Sakineh
authors: S
authors: Pirahmadi
authors: Akram A
authors: AA
authors: Mehrizi
authors: Navid D
authors: ND
authors: Djadid
mesh_terms: D000328:Adult; D001483:Base Sequence; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007113:Immunity, Innate; D007492:Iran / Q000453:epidemiology; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D010963:Plasmodium falciparum / Q000276:immunology / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D017472:Receptors, Interleukin-1 / Q000235:genetics*; D017422:Sequence Analysis, DNA; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D051217:Toll-Like Receptor 9 / Q000235:genetics*
chemical_list: D008562:Membrane Glycoproteins; D017472:Receptors, Interleukin-1; C434984:TIRAP protein, human; C495345:TLR4 protein, human; C495371:TLR9 protein, human; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9