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4 is associated with rapid progression of multiple sclerosis
From the Department of Neurology (Drs. Fazekas, Strasser-Fuchs, Hartung, Enzinger, and R. Schmidt) and the Institute of Medical Biochemistry (Dr. H. Schmidt), Karl-Franzens University, Graz; Department of Neurology (Drs. Kolleger, Schiefermeier, Schwarz, Kornek, and Vass), University of Vienna; Department of Neurology (Drs. Berger and Reindl) and Institute of Biostatistics (Dr. Pfeiffer), Leopold-Franzens University, Innsbruck; the SMZ-Ost Donauspital (Drs. Kristoferitsch, Grass, and Wimmer), Vienna; and the Ludwig Boltzmann-Institute for Molecular-Genetic Laboratory Diagnostics (Dr. Huber), SMZ-Ost Donauspital, Vienna, Austria.
Address correspondence and reprint requests to Franz Fazekas, MD, Department of Neurology and MRI Center, Karl-Franzens University, Auenbruggerplatz 22, A-8036 Graz, Austria; e-mail: franz.fazekas{at}kfunigraz.ac.at
Objective: — The apolipoprotein E (APOE) polymorphism is known to impact on various neurologic disorders and has differential effects on the immune system and on CNS repair. Previous findings concerning a possible modulation of the clinical course of MS have been inconsistent, however.
Methods: — In a cross-sectional study, the authors investigated 374 patients with clinically definite MS and a disease duration of at least 3 years and related their clinical and demographic findings to the allelic polymorphism of the APOE gene. The genotype distribution of patients with MS was compared with a cohort of 389 asymptomatic, randomly selected elderly volunteers.
Results: — The authors found no significant differences in the distribution of genotypes between patients with MS and controls. However, patients with MS with the 
4 allele (n = 85) had a significantly higher progression index of disability (0.46 ± 0.4 versus 0.33 ± 0.26; p < 0.004) and a worse ranked MS severity score (5.1 ± 1.9 versus 5.7 ± 1.7; p = 0.05) than their non-4 counterparts, despite significantly more frequent long-term immunotherapy in 4 carriers (74% versus 58%; p < 0.007). The annual relapse rate in 4 carriers (0.87 ± 0.56) was significantly higher than in patients with MS without an 4 allele (0.71 ± 0.47; p = 0.03).
Conclusions: — These results suggest no effect of the APOE genotype on susceptibility to MS, but indicate an association of the APOE 4 allele with a more severe course of the disease.
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|
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|
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|
|
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|
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|
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|
|
|
|
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|
|
|
|
|
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|
|
|
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|
|
|
|
 |
|
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|
|
|
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|
|
|
|
|
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|
|
|
|
 |
|
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|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
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|
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|
|
|
|
|
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|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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