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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).    Discussion  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.    Conclusion  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.

A common TLR1 polymorphism is associated with higher parasitaemia in a Southeast Asian population with Plasmodium falciparum malaria