Third-party-funded project
Title:
Identification of functional polymorphisms of disease modifying genes in MS patients
Project management at the University of Würzburg:
Participating scientists:
- Dr. med. M. Mäurer
, (Neurologie),Tel: 0931 201 23778,Fax: 0931 201 23488,Mail: mathias.maurer@mail.uni-wuerzburg.de
- Dr. rer. nat. N. Kruse
, (Neurologie, bis 05/2001),Tel: 0931 201 23548,Fax: 0931 201 23488,Mail: niels.kruse@web.de
- Dr. med. R. Gieß
, (Neurologie, bis 06/2001),Tel: 0931 201 24719,Fax: 0931 201 23488
- Prof. Dr. med. K. V. Toyka
,Tel: 0931 201 23751,Fax: 0931 201 23946,Mail: Toyka_K@klinik.uni-wuerzburg.de
Abstract:
DNA samples were collected from clinical well characterized MS patients, which attended our out-patients department for several years. First, we identified functional relevant gene polymorphisms in known immunoregulatory factors. The in vitro phenotypes of these mutations were investigated by appropriate functional tests and correlated to course of the disease, severity of symptoms and results of magnetic resonance images. First, we observed a correlation of the CTLA-4 (exon1+49) mutation with a reduced expression of this molecule on the surface of blood lymphocytes and chronic progressive disease course.
Furthermore, we looked for polymorphisms in neurotrophic factor genes and detected an association of a CNTF null mutation with early disease onset and severe course. Currently, we are establishing a new DNA collection of familiar MS cases together with Dr. B. Hemmer (Marburg).
Key words:
multiple sclerosis
genotype
genetic polymorphism
CTLA-4
CNTF
Projekt period:
from 01.2000 to 12.2001
Funding institution:
Landeshaushalt Wissenschaftsministerium ( BMBF ) ,Granting date: 18.12.1999
Publications:
- Mäurer, M., Kruse, N., Giess, R., Metzner, N., Kyriallis, K., Toyka, K., Rieckmann, P..
(1999). Gene polymorphism at position ?308 of the tumor necrosis factor alpha promotor is not associated with disease progression in multiple sclerosis. J. Neurol., 2,7. (scientific article)
- Mäurer, M., Kruse, N., Giess, R., Toyka, K.V., Rieckmann, P..
(2000). Genetic variation at position ?1082 of the interleukin 10 (IL-10) promotor and the outcome if multiple sclerosis. J. Neuroimmunol., 3,3. (scientific article)
- Hackstein, H., Bitsch, A., Bohnert, A., Hofmann, H., Weber, F., Linington, C., Mäurer, M., Poser, S., Rieckmann, P., Bein, G..
(2001). The interleukin-4 receptor variant R551 influences susceptibility to major clinical forms of multiple sclerosis.. J. Neuroimmunol., 3,3. (scientific article)
- Mäurer, M., Loserth, S., Kolb-Mäurer, A., Ponath, A., Wiese, S., Kruse, N., Rieckmann, P..
(2002). A polymorphism in the human cytotoxic T-lymphocyte antigen 4 (CTLA-4) gene (exon 1 +49) alters T-cell activation. Immunogenetics, 2,8. (scientific article)
- Mäurer M, Ponath A, Kruse N, Rieckmann P..
(2002). CTLA4 exon 1 dimorphism is associated with primary progressive multiple sclerosis. J. Neuroimmunol., 3,3. (scientific article)
- Kruse, N., Berg, D., Francis, M.J., Naumann, M., Rausch, W.D., Reiners, K., Rieckmann, P., Weishaupt, A., Becker, G..
(2001). Reduction of Menkes mRNA and copper in leukocytes of patients with primary adult-onset dystonia. Ann. Neurol., 8,5. (scientific article)
- Gieß, R., Mäurer, M., Gold, R., Toyka, K.V., Sendtner, M., Rieckmann, P..
(2002). A null mutation in the CNTF gene is associated with early onset of multiple sclerosis. Arch. Neurol., 4,1. (scientific article)
- Linker R, Mäurer M, Gaupp S, Martini R, Holtmann B, Giess R, Rieckmann P, Lassmann H, Toyka KV, Sendtner M, Gold R.
(2002). CNTF is a major protective factor in demyelinating CNS disease: a neurotrophic cytokine as modulator in neuroinflammation. Nature Med., 27,9. (scientific article)
