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Published on: April 4, 2018
Genetic variants in the tumor necrosis factor receptor II gene in patients with multiple sclerosis
R Ehling1, Ch Gassner, A Lutterotti
1Department of Neurology, University of Innsbruck, Anichstrasse, Innsbruck, Austria.
Abstract:
Common genetic variants have been shown to influence disease susceptibility, disease course, or both in multiple sclerosis (MS). Several studies have suggested a role for tumor necrosis factor-alpha (TNF-alpha) in the pathogenesis of MS. Recently, it has been reported that the TNF receptor (TNFR) II plays an essential role in the pathology and progression of experimental autoimmune encephalomyelitis, an animal model of MS. To investigate whether TNFR II polymorphisms influence susceptibility and/or clinical progression of MS, genomic DNA of 321 samples of the Austrian Genetics in MS study group and DNA of 174 platelet donors, who served as healthy controls, were genotyped for five polymorphic sites in the TNFR II gene: exon 6 nucleotide (nt) 676*T-->G, exon 6 nt 783*G-->A (both are associated with non-conserved amino acid substitution), exon 10 nt 1663*G-->A, exon 10 nt 1668*T-->G, and exon 10 nt 1690*T-->C (all of which are located in the 3' non-coding region of the gene). We found a significant association between exon 10 nt 1668*T-->G polymorphism and susceptibility to MS. The other investigated nucleotide substitutions were not associated with susceptibility to or clinical parameters in MS.
Insights
Genetic variations in the tumor necrosis factor receptor (TNFR) II gene may influence multiple sclerosis (MS) susceptibility. A specific polymorphism in exon 10 of the TNFR II gene was significantly associated with MS risk.
Area of Science:
- Genetics
- Immunology
- Neurology
Background:
- Genetic variants impact multiple sclerosis (MS) susceptibility and progression.
- Tumor necrosis factor-alpha (TNF-alpha) and its receptor (TNFR) II are implicated in MS pathogenesis.
- TNFR II plays a critical role in experimental autoimmune encephalomyelitis, an animal model for MS.
Purpose of the Study:
- To investigate the association between polymorphisms in the TNFR II gene and susceptibility to MS.
- To determine if TNFR II gene variations influence the clinical progression of MS.
Main Methods:
- Genotyping of 321 MS patients and 174 healthy controls for five polymorphic sites in the TNFR II gene.
- Analysis included exon 6 (nt 676 and nt 783) and exon 10 (nt 1663, nt 1668, and nt 1690) polymorphisms.
- Statistical analysis to correlate genotypes with MS susceptibility and clinical parameters.
Main Results:
- A significant association was found between the exon 10 nt 1668*T-->G polymorphism and susceptibility to MS.
- No significant associations were observed for the other four investigated TNFR II gene polymorphisms with MS susceptibility.
- None of the studied TNFR II polymorphisms were associated with clinical parameters in MS patients.
Conclusions:
- The exon 10 nt 1668*T-->G polymorphism in the TNFR II gene is a potential genetic marker for MS susceptibility.
- Further research is warranted to elucidate the functional impact of this specific TNFR II polymorphism on MS development.
- TNFR II gene variants may contribute to the genetic predisposition of multiple sclerosis.
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