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

Attila L Szvetko, Ashleigh Jones, Jason Mackenzie, Lotti Tajouri, Peter A Csurhes, Judith M Greer, Michael P. Pender, Lyn R. Griffiths

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)438-41
Number of pages4
JournalNeurological Research
Volume32
Issue number4
DOIs
Publication statusPublished - May 2010

Fingerprint

Multiple Sclerosis
Toll-Like Receptors
Genotype
Genes
Genotyping Techniques
Toll-Like Receptor 3
Central Nervous System Diseases
Capillary Electrophoresis
Autoimmunity
Gene Frequency
Base Pairing
Population
Young Adult
Central Nervous System
Gels
Alleles
Viruses
Inflammation
T-Lymphocytes
human TLR3 protein

Cite this

Szvetko, Attila L ; Jones, Ashleigh ; Mackenzie, Jason ; Tajouri, Lotti ; Csurhes, Peter A ; Greer, Judith M ; Pender, Michael P. ; Griffiths, Lyn R. / Investigation of the [-/A]8 and C1236T genetic variations within the human Toll-like receptor 3 gene for association with multiple sclerosis. In: Neurological Research. 2010 ; Vol. 32, No. 4. pp. 438-41.
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abstract = "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.",
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Investigation of the [-/A]8 and C1236T genetic variations within the human Toll-like receptor 3 gene for association with multiple sclerosis. / Szvetko, Attila L; Jones, Ashleigh; Mackenzie, Jason; Tajouri, Lotti; Csurhes, Peter A; Greer, Judith M; Pender, Michael P.; Griffiths, Lyn R.

In: Neurological Research, Vol. 32, No. 4, 05.2010, p. 438-41.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Szvetko, Attila L

AU - Jones, Ashleigh

AU - Mackenzie, Jason

AU - Tajouri, Lotti

AU - Csurhes, Peter A

AU - Greer, Judith M

AU - Pender, Michael P.

AU - Griffiths, Lyn R.

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AB - 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.

U2 - 10.1179/174313209X405155

DO - 10.1179/174313209X405155

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JO - Neurological Research

JF - Neurological Research

SN - 0161-6412

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