title: Association between Toll-like receptor 2 (TLR2) polymorphisms and asymptomatic bancroftian filariasis.
abstract: Lymphatic filariasis is mainly caused by the filarial nematodes Wuchereria bancrofti and Brugia malayi. Wolbachia, intracellular symbiotic bacteria in filarial parasite, is known to induce immune response predominantly through Toll-like receptor 2 (TLR2). This study was performed to investigate the association between polymorphisms of the TLR2 gene and susceptibility to asymptomatic bancroftian filariasis. A total of 142 unrelated asymptomatic bancroftian filariasis patients and 151 endemic normal controls in Tak province, Thailand were recruited into this study. The -196 to -173 deletion (del) polymorphism in the 5' untranslated region was investigated by allele-specific polymerase chain reaction. Two single nucleotide polymorphisms, +597 T>C and +1350 T>C, in exon 3 were identified by polymerase chain reaction-restriction fragment length polymorphism analysis. Furthermore, we analyzed the functional difference between the TLR2 -196 to -173 del and wild-type (wt) alleles using the luciferase reporter assay. All three polymorphisms were associated with a higher risk of asymptomatic bancroftian filariasis and were in strong linkage disequilibrium with each other. The TLR2 haplotype -196 to -173del/+597C/+1350C was strongly associated with an increased risk of asymptomatic bancroftian filariasis. The TLR2 -196 to -173 del allele had a significantly lower transcriptional activity than wt allele. The results of our study indicate that TLR2 -196 to -173 del, +597 T>C and +1350 T>C polymorphisms are associated with asymptomatic bancroftian filariasis in Thailand. Our functional study also supports this finding with respect to differential TLR2 gene expression by -196 to -173 del polymorphism.
authors.affiliation: Lymphatic Filariasis Research Unit, Department of Parasitology and Chulalongkorn Medical Research Center (Chula MRC), Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand, au_junpee@yahoo.com.
authors.forename: Alisa
authors.initials: A
authors.lastname: Junpee
authors.forename: Tewin
authors.initials: T
authors.lastname: Tencomnao
authors.forename: Vivornpun
authors.initials: V
authors.lastname: Sanprasert
authors.forename: Surang
authors.initials: S
authors.lastname: Nuchprayoon
mesh_terms: D020121:5' Untranslated Regions; D000293:Adolescent; D000328:Adult; D000818:Animals; D005260:Female; D005368:Filariasis / Q000235:genetics* / Q000276:immunology / Q000469:parasitology*; D005787:Gene Frequency; D017930:Genes, Reporter; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D017384:Sequence Deletion; D013785:Thailand; D051195:Toll-Like Receptor 2 / Q000235:genetics* / Q000276:immunology; D014158:Transcription, Genetic; D014958:Wuchereria bancrofti / Q000276:immunology* / Q000472:pathogenicity; D055815:Young Adult
chemical_list: D020121:5' Untranslated Regions; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D008156:Luciferases