title: A common TLR1 polymorphism is associated with higher parasitaemia in a Southeast Asian population with Plasmodium falciparum malaria.
abstract: BACKGROUND
  The factors leading to poor outcomes in malaria infection are incompletely understood. Common genetic variation exists in the human genes for Toll like receptors (TLRs) that alter host responses to pathogen-associated molecular patterns. Genetic variation in TLR1 and TLR6 could alter the risk of development of complicated malaria and ability of the host to control the parasite burden during acute Plasmodium falciparum infection.
  
  
  METHODS
  Five single nucleotide polymorphisms in TLR1 and TLR6 in 432 patients with clinical P. falciparum monoinfection acquired on the Thai-Myanmar border were genotyped. Using logistic regression, associations with the development of complicated malaria and the percentage of infected erythrocytes (parasitaemia) on the day of presentation to clinical care (day zero) were tested.
  
  
  RESULTS
  Genotypes carrying the T (major) allele of TLR1 rs5743551--an allele associated with improved outcomes in sepsis--were associated with higher parasitaemia measured on day zero (p = 0.03).
  
  
  CONCLUSIONS
  Since malaria exerts strong genetic pressure on the human genome, protection from parasitaemia associated with TLR1 rs5743551 may account for the maintenance of an allele associated with poor outcomes in Caucasians with sepsis.
  
  
  CONCLUSIONS
  These data suggest that genetic variation in TLR1 has effects on the host response to Plasmodium falciparum malaria in Asian populations. Genotypes from TLR6 showed no evidence of association with either complicated malaria or parasite burden.
authors.affiliation: Division of Allergy and Infectious Diseases, Department of Medicine, Harborview Medical Center, University of Washington, Box 359640, Seattle, WA, USA. willhahn@uw.edu.
authors.forename: William O
authors.initials: WO
authors.lastname: Hahn
authors.affiliation: Division of Pulmonary Critical Care Medicine, Department of Medicine, Harborview Medical Center, University of Washington, Seattle, WA, USA. SHarju-Baker@medicine.washington.edu.
authors.forename: Susanna
authors.initials: S
authors.lastname: Harju-Baker
authors.affiliation: Tropical Disease Unit, Department of Medicine, University Health Network-Toronto General Hospital, Toronto, Ontario, Canada. laura.erdman@utoronto.ca.|SAR Laboratories, Sandra Rotman Centre for Global Health, University of Toronto, Toronto, Ontario, Canada. laura.erdman@utoronto.ca.
authors.forename: Laura K
authors.initials: LK
authors.lastname: Erdman
authors.affiliation: Clinical Malaria Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. srivicha.kru@mahidol.ac.th.
authors.forename: Srivicha
authors.initials: S
authors.lastname: Krudsood
authors.affiliation: Tropical Disease Unit, Department of Medicine, University Health Network-Toronto General Hospital, Toronto, Ontario, Canada. Kevin.Kain@uhn.ca.|SAR Laboratories, Sandra Rotman Centre for Global Health, University of Toronto, Toronto, Ontario, Canada. Kevin.Kain@uhn.ca.
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Kain
authors.affiliation: Division of Allergy and Infectious Diseases, Department of Medicine, Harborview Medical Center, University of Washington, Box 359640, Seattle, WA, USA. MWurfel@medicine.washington.edu.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Wurfel
authors.affiliation: Division of Allergy and Infectious Diseases, Department of Medicine, Harborview Medical Center, University of Washington, Box 359640, Seattle, WA, USA. WCLiles@medicine.washington.edu.
authors.forename: Wayne C
authors.initials: WC
authors.lastname: Liles
mesh_terms: D000293:Adolescent; D000328:Adult; D001210:Asia, Southeastern / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006801:Humans; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D018512:Parasitemia / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D051194:Toll-Like Receptor 1 / Q000235:genetics*; D051216:Toll-Like Receptor 6 / Q000235:genetics*; D055815:Young Adult
chemical_list: D051194:Toll-Like Receptor 1; D051216:Toll-Like Receptor 6