title: The TLR2 and TLR4 gene polymorphisms in Moroccan visceral leishmaniasis patients.
abstract: Visceral leishmaniasis (VL) is endemic in the Mediterranean basin and leads to the most severe form of Leishmania infection, lethal if left untreated. However, most infections are sub-clinical or asymptomatic, reflecting the influence of host genetic background on disease outcome. This study aimed to investigate possible association of TLR4 Asp299Gly, TLR4 Thr399Ile and TLR2 Arg753Gln polymorphisms with VL in Moroccan children. We enrolled 119 children with VL caused by Leishmania infantum as well as 138 unrelated children, 95 asymptomatic subjects and 43 healthy individuals who had no evidence of present or past infection. Polymorphisms were genotyped by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and amplification refractory mutation system assay (ARMS-PCR). Results showed significant differences in genotype Thr399Ile and recessive model frequencies between VL and delayed-type hypersensitivity (DTH+) groups (p=0.018, OR=0.414CI 0.195-0.880; p=0.029, OR=0.448CI 0.214-0.938], respectively) by having the amino-acid threonine polymorphism as a reference in the VL group. Concerning the Asp299Gly there were a significant associations when comparing VL vs DTH+ (Asp299Gly genotype p=0.002, OR=0.326CI 0.158-0.671, allele frequencies p=0.033, OR=0.396CI 0.164-0.959, recessive model p=0.002, OR=0.343CI 0.172-0.681) and DTH+ vs DTH- groups (Asp299Gly genotype p=2.160E-4, OR=3.065CI 1.672-5.618, Gly299Gly genotype p=0.047, OR=0.368CI 0.299-0.452, allele frequencies p=1.406E-7, OR=29.571CI 3.907-223.8, recessive model p=4.370E-14, OR=36.965CI 8.629-158.3), by having the aspartic acid polymorphism as a reference these results suggest that the allele A (savage) confer protection against the clinical manifestations but not against the infection. Furthermore, there was a significant association regarding the Arg753Gln genotype (p=0.002, OR=0.326CI 0.158-0.671), allele frequencies (p=0.033, OR=0.396CI 0.164-0.959) and when applying a recessive model (p=0.002, OR=0.343CI 0.172-0.681) in the VL vs DTH+ groups. The same results was observed when comparing DTH+ vs DTH- groups (p=4.136E-6, OR=0.211CI 0.104-0.428), allele frequencies (p=0.008, OR=0.327CI 0.137-0.779) and recessive model (p=1.748E-5, OR=0.244CI 0.124-0.480). The results provide evidence that allele C in Thr399Ile and allele G in Arg753Gln polymorphisms may lead to protection against the clinical disease. Our data provide insights into the possible role of TLR2 and TLR4 variations in VL susceptibility.
authors.affiliation: Laboratory of Parasitology and Vector-Borne-Diseases, Institut Pasteur du Maroc, Casablanca, Morocco; Laboratory of Genetic, Neuroendocrinology and Biotechnology, Faculty of Science, University Ibn Tofaïl, B.P 133, 14 000 Kénitra, Morocco.
authors.forename: Rajaâ
authors.initials: R
authors.lastname: Ejghal
authors.affiliation: Faculty of Medicine and Pharmacy, University Sidi Mohammed Ben Abdellah, Route de Sefrou, Fes, Morocco.
authors.forename: Moustapha
authors.initials: M
authors.lastname: Hida
authors.affiliation: Hospital Ibn Al Khatib, Pediatric Department, Fes, Morocco.
authors.forename: Mounya Lahkim
authors.initials: ML
authors.lastname: Bennani
authors.affiliation: Hospital Ibn Al Khatib, Pediatric Department, Fes, Morocco.
authors.forename: Mariame
authors.initials: M
authors.lastname: Meziane
authors.affiliation: Hospital Ibn Al Khatib, Pediatric Department, Fes, Morocco.
authors.forename: Rabia
authors.initials: R
authors.lastname: Aurag
authors.affiliation: Laboratory of Parasitology and Vector-Borne-Diseases, Institut Pasteur du Maroc, Casablanca, Morocco. Electronic address: meryem.lemrani@pasteur.ma.
authors.forename: Meryem
authors.initials: M
authors.lastname: Lemrani
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004198:Disease Susceptibility; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007223:Infant; D018314:Leishmania infantum / Q000235:genetics*; D007898:Leishmaniasis, Visceral / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D009018:Morocco / Q000453:epidemiology; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D051195:Toll-Like Receptor 2 / Q000235:genetics*; D051197:Toll-Like Receptor 4 / Q000235:genetics*
chemical_list: D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4
keywords: Asymptomatic infection; Host susceptibility; Moroccan children; TLR4 and TLR2 polymorphisms; Visceral leishmaniasis