Association of Toll-like receptor 2Arg 753Gln and Toll-like receptor 1Ile 602Ser single-nucleotide polymorphisms with leptospirosis in anargentine population

Abstract

Toll-like receptor 2 (TLR2), a member of the Toll-like receptor family, plays an50 important role in the recognition of and subsequent immune response activation51 against leptospirosis in humans. The genetic polymorphism in TLR2 of an arginine to52 glutamine substitution at residue 753 (Arg753Gln) has been associated with a53 negative influence on TLR2 function, which may, in turn, determine the innate host54 response to Leptospira spp. This bacterium signals through TLR2/TLR155 heterodimers in human cells. The aim of the present study was to investigate the56 Arg753Gln single-nucleotide polymorphism (SNP) of the TLR2 gene, and the57 isoleucine to serine transversion at position 602 (Ile602Ser) of the TLR1 gene58 (previously associated with Lyme disease), in leptospirosis patients compared to59 healthy controls, carrying out a retrospective case/control study. The TLR260 polymorphism adenine (A) allele was observed in 7.3% of leptospirosis patients but61 was not found in the control group, whereas the guanine (G) allele of the TLR162 polymorphism was found in 63.6% of patients and 41.6% of controls. Susceptibility to63 leptospirosis disease was increased 10.57-fold for carriers of the TLR2 G/A64 genotype (P=0.0493) and 3.85-fold for carriers of the TLR1 G/G genotype65 (P=0.0428). Furthermore, the risk of developing hepatic insufficiency and jaundice66 was increased 18.86- and 27.60-fold for TLR2 G/A carriers, respectively. Similarly,67 the risk of developing jaundice was increased 12.67-fold for TLR1 G allele carriers68 (G/G and T/G genotypes). In conclusion, the present data suggest that the TLR269 Arg753Gln and TLR1 Ile602Ser SNPs influence the risk of developing leptospirosis70 and its severity.