title: Association of Toll-like receptor 2 Arg753Gln and Toll-like receptor 1 Ile602Ser single-nucleotide polymorphisms with leptospirosis in an Argentine population.
abstract: Toll-like receptor 2 (TLR2), a member of the Toll-like receptor family, plays an important role in the recognition of and subsequent immune response activation against leptospirosis in humans. The genetic polymorphism in TLR2 of an arginine to glutamine substitution at residue 753 (Arg753Gln) has been associated with a negative influence on TLR2 function, which may, in turn, determine the innate host response to Leptospira spp. This bacterium signals through TLR2/TLR1 heterodimers in human cells. The aim of the present study was to investigate the Arg753Gln single-nucleotide polymorphism (SNP) of the TLR2 gene, and the isoleucine to serine transversion at position 602 (Ile602Ser) of the TLR1 gene (previously associated with Lyme disease), in leptospirosis patients compared to healthy controls, carrying out a retrospective case/control study. The TLR2 polymorphism adenine (A) allele was observed in 7.3% of leptospirosis patients but was not found in the control group, whereas the guanine (G) allele of the TLR1 polymorphism was found in 63.6% of patients and 41.6% of controls. Susceptibility to leptospirosis disease was increased 10.57-fold for carriers of the TLR2 G/A genotype (P=0.0493) and 3.85-fold for carriers of the TLR1 G/G genotype (P=0.0428). Furthermore, the risk of developing hepatic insufficiency and jaundice was increased 18.86- and 27.60-fold for TLR2 G/A carriers, respectively. Similarly, the risk of developing jaundice was increased 12.67-fold for TLR1 G allele carriers (G/G and T/G genotypes). In conclusion, the present data suggest that the TLR2 Arg753Gln and TLR1 Ile602Ser SNPs influence the risk of developing leptospirosis and its severity.
authors.affiliation: Laboratory of Animal Viruses, Institute of Biotechnology and Molecular Biology, CCT-La Plata, CONICET-UNLP, 1900 La Plata, Buenos Aires, Argentina.
authors.forename: Maia
authors.initials: M
authors.lastname: Cédola
authors.affiliation: National Institute of Respiratory Diseases, ANLIS-UNL, Santa Fe, 3000 Santa Fe, Argentina.
authors.forename: Yosena
authors.initials: Y
authors.lastname: Chiani
authors.affiliation: Laboratory of Animal Viruses, Institute of Biotechnology and Molecular Biology, CCT-La Plata, CONICET-UNLP, 1900 La Plata, Buenos Aires, Argentina.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Pretre
authors.affiliation: Laboratory of Animal Viruses, Institute of Biotechnology and Molecular Biology, CCT-La Plata, CONICET-UNLP, 1900 La Plata, Buenos Aires, Argentina.
authors.forename: Lucrecia
authors.initials: L
authors.lastname: Alberdi
authors.affiliation: National Institute of Respiratory Diseases, ANLIS-UNL, Santa Fe, 3000 Santa Fe, Argentina.
authors.forename: Bibiana
authors.initials: B
authors.lastname: Vanasco
authors.affiliation: Laboratory of Animal Viruses, Institute of Biotechnology and Molecular Biology, CCT-La Plata, CONICET-UNLP, 1900 La Plata, Buenos Aires, Argentina. Electronic address: rmg1426@gmail.com.
authors.forename: Ricardo M
authors.initials: RM
authors.lastname: Gómez
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001118:Argentina; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D007223:Infant; D007922:Leptospirosis / Q000235:genetics* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D051194:Toll-Like Receptor 1 / Q000235:genetics* / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000235:genetics* / Q000276:immunology; D055815:Young Adult
chemical_list: D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2
keywords: Arg753Gln; Human TLR1; Human TLR2; Ile602Ser; Leptospirosis; SNP