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Investigation of bax, bcl-2, bcl-x and p53 gene polymorphisms in multiple sclerosis
T Kuhlmann1, M Glas, C zum Bruch
1Department of Neuropathology, Charité, Campus Virchow-Klinikum, Humboldt-Universität, Augustenburger Platz 1, 13353, Berlin, Germany.
Abstract:
Clinical course, outcome, radiological features, severity, and histopathology are heterogenous in multiple sclerosis (MS). Since MS is considered to be a polygenic disease, the genetic background may at least partly be responsible for this variability. Some MS cases are histopathologically characterized by a dramatic oligodendrocyte loss that is in part caused by apoptosis. A dysregulated apoptotic elimination of self-reactive T cells may also contribute to disease susceptibility. To analyze genetic differences in the apoptosis regulating factors bcl-2, bax, bcl-x and p53 we investigated polymorphisms of these genes in 105 patients with a relapsing remitting disease course and 99 controls by PCR-SSCP and direct sequencing. We identified so far unpublished sequence alterations in the promotor region of the bxl-x gene, in exon 7 of the p53 gene, and in exon 1 of the bax gene. No differences were observed between MS patients and controls. Additional known polymorphisms were found in intron 3 of the bax gene and in exon 6 of the p53 gene. No significant differences in the frequency of gene sequence variations were found between MS patients and controls. The apoptosis genes studied here therefore appear less likely to be important effector genes in MS.
Insights
Genetic variations in apoptosis-regulating genes (bcl-2, bax, bcl-x, p53) were examined in multiple sclerosis (MS) patients. No significant differences were found between patients and controls, suggesting these genes are unlikely major contributors to MS.
Area of Science:
- Neuroimmunology
- Genetics
- Cell Biology
Background:
- Multiple sclerosis (MS) exhibits significant heterogeneity in clinical presentation, radiological findings, and histopathology.
- This variability may stem from genetic factors, as MS is considered a polygenic disease.
- Apoptosis, or programmed cell death, plays a role in MS pathogenesis, including oligodendrocyte loss and potential dysregulation of self-reactive T cell elimination.
Purpose of the Study:
- To investigate potential genetic associations between polymorphisms in apoptosis-regulating genes (bcl-2, bax, bcl-x, p53) and multiple sclerosis.
- To identify novel sequence variations in these genes within an MS patient cohort.
Main Methods:
- Genotyping of apoptosis-related genes (bcl-2, bax, bcl-x, p53) using PCR-SSCP and direct sequencing.
- Analysis of gene polymorphisms in 105 relapsing-remitting MS patients and 99 healthy controls.
Main Results:
- Novel sequence alterations were identified in the bcl-x, p53, and bax genes.
- Known polymorphisms in bax and p53 genes were also observed.
- No significant differences in the frequency of investigated gene sequence variations were detected between MS patients and controls.
Conclusions:
- The studied apoptosis-regulating genes (bcl-2, bax, bcl-x, p53) do not appear to be major effector genes contributing to the genetic susceptibility or variability in multiple sclerosis.
- Further research into other genetic factors influencing MS pathogenesis is warranted.