title: Investigation of bax, bcl-2, bcl-x and p53 gene polymorphisms in multiple sclerosis.
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 We identified so far unpublished sequence alterations in the promotor region of the bxl-x gene, in exon 7 of the p53 gene, and in exon 1 of the bax gene.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.
authors.affiliation: Department of Neuropathology, Charité, Campus Virchow-Klinikum, Humboldt-Universität, Augustenburger Platz 1, 13353, Berlin, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Kuhlmann
authors.forename: M
authors.initials: M
authors.lastname: Glas
authors.forename: C
authors.initials: C
authors.lastname: zum Bruch
authors.forename: W
authors.initials: W
authors.lastname: Mueller
authors.forename: A
authors.initials: A
authors.lastname: Weber
authors.forename: F
authors.initials: F
authors.lastname: Zipp
authors.forename: W
authors.initials: W
authors.lastname: Brück
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence / Q000235:genetics; D003062:Codon / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics; D019254:Genes, bcl-2 / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D006801:Humans; D007438:Introns / Q000235:genetics; D009103:Multiple Sclerosis / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D013601:T-Lymphocytes / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
chemical_list: C494826:BAX protein, human; C494811:BCL2L1 protein, human; D003062:Codon; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein