Document Detail

Variants in the toll-like receptor signaling pathway and clinical outcomes of malaria.
MedLine Citation:
PMID:  18662133     Owner:  NLM     Status:  MEDLINE    
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.
Fabiana M S Leoratti; Lilian Farias; Fabiana P Alves; Martha C Suarez-Mútis; José R Coura; Jorge Kalil; Erney P Camargo; Sandra L Moraes; Rajendranath Ramasawmy
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of infectious diseases     Volume:  198     ISSN:  0022-1899     ISO Abbreviation:  J. Infect. Dis.     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-08-12     Completed Date:  2008-09-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0413675     Medline TA:  J Infect Dis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  772-80     Citation Subset:  AIM; IM    
Instituto de Medicina Tropical de São Paulo, University of São Paulo, São Paulo, Brazil.
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MeSH Terms
Antimalarials / therapeutic use
Case-Control Studies
Gene Expression Regulation
Gene Frequency
Genetic Predisposition to Disease
Malaria / drug therapy,  immunology,  metabolism*
Odds Ratio
Parasitemia / parasitology
Polymorphism, Single Nucleotide*
Signal Transduction / genetics*,  physiology
Toll-Like Receptors / genetics*,  metabolism
Reg. No./Substance:
0/Antimalarials; 0/Toll-Like Receptors

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