title: Very low frequencies of Toll-like receptor 2 supposed-2029T and 2258A (RS5743708) mutant alleles in southern Brazilian critically ill patients: would it be a lack of worldwide-accepted clinical applications of Toll-like receptor 2 variants?
abstract: Toll-like receptor 2 (TLR2) is a recognition receptor for the widest repertoire of pathogen-associated molecular patterns. Two polymorphisms of TLR2 could be linked to reduced nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) activation and to increased risk of infection (supposed-2029C>T and 2258G>A). We investigated the supposed-2029C>T and 2258G>A TLR2 polymorphisms in 422 critically ill patients of European origin from southern Brazil (295 with sepsis and 127 without sepsis) and reviewed 33 studies on these polymorphisms, conducting a quality assessment with a score system. Among our patients we found only one heterozygote (1/422) for the supposed-2029C>T and none for the 2258G>A (0/422) single nucleotide polymorphism (SNP). We were unable to find a clinical application of supposed-2029T and 2258A allele analyses in our southern Brazilian population. Our review detected that current TLR2 SNP assays had very controversial and contradictory results derived from reports with a variety of investigation quality criteria. We suggest that, if analyzed alone, the supposed-2029C>T and 2258G>A TLR2 SNP are not good candidates for genetic markers in studies that search for direct or indirect clinical applications between genotype and phenotype. Future efforts to improve the knowledge and to provide other simultaneous genetic markers might reveal a more effective TLR2 effect on the susceptibility to infectious diseases.
authors.affiliation: Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Helena Strelow
authors.initials: HS
authors.lastname: Thurow
authors.forename: Cladinara Roberts
authors.initials: CR
authors.lastname: Sarturi
authors.forename: Paulo Roberto Vargas
authors.initials: PR
authors.lastname: Fallavena
authors.forename: Francis Jackson de Oliveira
authors.initials: FJ
authors.lastname: Paludo
authors.forename: Juliane Bentes
authors.initials: JB
authors.lastname: Picanço
authors.forename: Lucas Rosa
authors.initials: LR
authors.lastname: Fraga
authors.forename: Pietra
authors.initials: P
authors.lastname: Graebin
authors.forename: Vinícius Carolino
authors.initials: VC
authors.lastname: de Souza
authors.forename: Fernando Suparregui
authors.initials: FS
authors.lastname: Dias
authors.forename: Otávio de Tolêdo
authors.initials: Ode T
authors.lastname: Nóbrega
authors.forename: Clarice Sampaio
authors.initials: CS
authors.lastname: Alho
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001938:Brazil; D003141:Communicable Diseases / Q000150:complications / Q000235:genetics; D016638:Critical Illness; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D018805:Sepsis / Q000209:etiology / Q000235:genetics*; D051195:Toll-Like Receptor 2 / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D051195:Toll-Like Receptor 2