Investigation of the [-/A]8 and C1236T genetic variations within the human Toll-like receptor 3 gene for association with multiple sclerosis

• Published in: Neurological research (New York) Vol. 32; no. 4; p. 438
• Main Authors: Szvetko, Attila L, Jones, Ashleigh, Mackenzie, Jason, Tajouri, Lotti, Csurhes, Peter A, Greer, Judith M, Pender, Michael P, Griffiths, Lyn R
• Format: Journal Article
• Language: English
• Published: England 01.05.2010
• Subjects: Adult; Australia; Base Pairing; DNA Mutational Analysis; Female; Gene Frequency - genetics; Genetic Predisposition to Disease - genetics; Genetic Testing; Genetic Variation - genetics; Genotype; Humans; Male; Middle Aged; Multigene Family; Multiple Sclerosis - diagnosis; Multiple Sclerosis - genetics; Multiple Sclerosis - metabolism; Toll-Like Receptor 3 - genetics; Australia
• ISSN: 1743-1328
• DOI: 10.1179/174313209X405155

Multiple sclerosis (MS) is a serious cause of neurological disability among young adults. The clinical course remains difficult to predict, and the pathogenesis of the disease is still modestly understood. Autoimmunity is thought to be a key aspect of the disease, with autoreactive T cells thought to mediate central nervous system (CNS) inflammation to some extent. Toll-like receptors are known to mediate cellular recognition of pathogens by way of patterns of molecular presentation. Toll-like receptor 3 is coded by the gene TLR3 and is recognized as an important factor in virus recognition and is known to be involved in the expression of neuroprotective mediators. We set out to investigate two variations within the TLR3 gene, an 8 bp insertion-deletion [-/A](8) and a single base-pair variation C1236T, in subjects with MS and matched healthy controls to determine whether significant differences exist in these markers in an Australian population. We used capillary gel electrophoresis and TaqMan genotyping assay techniques to resolve genotypes for each marker, respectively. Our work found no significant difference between frequencies for TLR3 [-/A](8) by genotype (chi(2)=1.03, p=0.60) or allele (chi(2)=1.09, p=0.30). Similarly, we found no evidence for the association of TLR3 C1236T by genotype (chi(2)=0.35, p=0.84) or allele frequency (chi(2)=0.31, p=0.58). This work reveals no evidence to suggest that these markers are associated with MS in the tested population. Although the role of TLR3 and the wider toll-like receptor family remain significant in neurological and CNS inflammatory disorders, our current work does not support a role for the two tested variants in this gene with regard to MS susceptibility.