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.