BACKGROUND: Malaria is one of the most significant infectious diseases in the world and is responsible for a large proportion of infant deaths. Toll-like receptors (TLRs), key components of innate immunity, are central to countering infection. Variants in the TLR-signaling pathway are associated with susceptibility to infectious diseases. METHODS: We genotyped single nucleotide polymorphisms (SNPs) of the genes associated with the TLR-signaling pathway in patients with mild malaria and individuals with asymptomatic Plasmodium infections by means of polymerase chain reaction. RESULTS: Genotype distributions for the TLR-1 I602S differed significantly between patients with mild malaria and persons with asymptomatic infection. The TLR-1 602S allele was associated with an odds ratio (OR) of 2.2 (P= .003; P(corrected)= .015) for malaria among patients with mild malaria due to any Plasmodium species and 2.1 (P= .015; P(corrected)= .75) among patients with mild malaria due to Plasmodium falciparum only. The TLR-6 S249P SNP showed an excess of homozygotes for the TLR-6 249P allele in asymptomatic persons, compared with patients with mild malaria due to any Plasmodium species (OR 2.1; 95% confidence interval [CI], 1.1- 4.2; P= .01; P(corrected)= .05), suggesting that the TLR-6 249S allele may be a risk factor for malaria (OR, 2.0; 95% CI, 1.1-3.7; P=0.01; P(corrected)= .05). The TLR-9 -1486C allele showed a strong association with high parasitemia (P< .001). CONCLUSIONS: Our findings indicate that the TLR-1 and TLR-6 variants are significantly associated with mild malaria, whereas the TLR-9-1486C/T variants are associated with high parasitemia. These discoveries may bring additional understanding to the pathogenesis of malaria.
BACKGROUND:Malaria is one of the most significant infectious diseases in the world and is responsible for a large proportion of infant deaths. Toll-like receptors (TLRs), key components of innate immunity, are central to countering infection. Variants in the TLR-signaling pathway are associated with susceptibility to infectious diseases. METHODS: We genotyped single nucleotide polymorphisms (SNPs) of the genes associated with the TLR-signaling pathway in patients with mild malaria and individuals with asymptomatic Plasmodium infections by means of polymerase chain reaction. RESULTS: Genotype distributions for the TLR-1I602S differed significantly between patients with mild malaria and persons with asymptomatic infection. The TLR-1 602S allele was associated with an odds ratio (OR) of 2.2 (P= .003; P(corrected)= .015) for malaria among patients with mild malaria due to any Plasmodium species and 2.1 (P= .015; P(corrected)= .75) among patients with mild malaria due to Plasmodium falciparum only. The TLR-6S249P SNP showed an excess of homozygotes for the TLR-6 249P allele in asymptomatic persons, compared with patients with mild malaria due to any Plasmodium species (OR 2.1; 95% confidence interval [CI], 1.1- 4.2; P= .01; P(corrected)= .05), suggesting that the TLR-6 249S allele may be a risk factor for malaria (OR, 2.0; 95% CI, 1.1-3.7; P=0.01; P(corrected)= .05). The TLR-9 -1486C allele showed a strong association with high parasitemia (P< .001). CONCLUSIONS: Our findings indicate that the TLR-1 and TLR-6 variants are significantly associated with mild malaria, whereas the TLR-9-1486C/T variants are associated with high parasitemia. These discoveries may bring additional understanding to the pathogenesis of malaria.
Authors: Nadia A Sam-Agudu; Jennifer A Greene; Robert O Opoka; James W Kazura; Michael J Boivin; Peter A Zimmerman; Melissa A Riedesel; Tracy L Bergemann; Lisa A Schimmenti; Chandy C John Journal: Am J Trop Med Hyg Date: 2010-04 Impact factor: 2.345
Authors: Saad M Bin Dajem; Adel Ali H Al-Sheikh; Marie Fe Bohol; Mohammad Alhawi; Mohammed N Al-Ahdal; Ahmed Al-Qahtani Journal: Parasitol Res Date: 2011-02-25 Impact factor: 2.289
Authors: Elly O Munde; Winnie A Okeyo; Samwel B Anyona; Evans Raballah; Stephen Konah; Wilson Okumu; Lilian Ogonda; John Vulule; Collins Ouma Journal: Infect Immun Date: 2012-10-08 Impact factor: 3.441
Authors: Susana Campino; Julian Forton; Sarah Auburn; Andrew Fry; Mahamadou Diakite; Anna Richardson; Jeremy Hull; Muminatou Jallow; Fatou Sisay-Joof; Margaret Pinder; Malcolm E Molyneux; Terrie E Taylor; Kirk Rockett; Taane G Clark; Dominic P Kwiatkowski Journal: Malar J Date: 2009-03-13 Impact factor: 2.979
Authors: Oliver C Jann; Annemarie King; Nestor Lopez Corrales; Susan I Anderson; Kirsty Jensen; Tahar Ait-Ali; Haizhou Tang; Chunhua Wu; Noelle E Cockett; Alan L Archibald; Elizabeth J Glass Journal: BMC Genomics Date: 2009-05-11 Impact factor: 3.969