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Apo E in multiple sclerosis and optic neuritis: the Apo E-o4 allele is associated with progression of multiple sclerosis

Department of Neurology, Glostrup Hospital University of Copenhagen, DK-2600 Glostrup, Denmark

J L Frederiksen

Department of Neurology, Glostrup Hospital University of Copenhagen, DK-2600 Glostrup, Denmark, jefr{at}glostruphosp.kbhamt.dk

P S Andersen

Department of Clinical Biochemistry, Statens Serum Institut, DK-2300 Copenhagen S, Denmark

M Christiansen

Department of Clinical Biochemistry, Statens Serum Institut, DK-2300 Copenhagen S, Denmark

Objective: To investigate the association between apolipoprotein E (Apo E) genotype in multiple sclerosis (MS) and acute monosymptomatic optic neuritis (ON) in a genetically homogeneous population with a high frequency of the Apo o4 allele. Background: The association between heterozygosity of Apo o4 and the development of MS is thoroughly investigated, while the association between homozygosity of Apo o4 and the development of MS is insufficiently studied. The association between Apo E genotype and disease progression remains controversial. Methods: 475 patients were included, 385 with MS and 90 with ON, consecutively seen in the MS clinic in the County of Copenhagen. Clinical data were obtained from medical records and degree of disability was determined prospectively using the Kurtzke expanded disability status scale (EDSS). Blood samples were used for Apo E genotyping. Disease progression was evaluated by the progression index (PI=EDSS/disease duration). Apo E genotype distribution was compared with 361 healthy controls. Results: The Apo o genotype distribution in the MS and ON groups was similar to the controls. The rate of disease progression in the group of MS patients with a disease duration of 10 years or less was significantly faster in the Apo o4 positive group (heterozygosity and homozygosity for Apo o4) (PI=1.41) compared to the Apo o4 negative group (PI=0.92) (P=0.009). Observing the MS subgroups, we found that the group of patients with RRMS had a faster rate of disease progression in the Apo o4 positive group (PI=1.12) compared to the Apo o4 negative group (PI=0.77) (P=0.024). Conclusions: Apo E genotypes do not influence the development of MS and ON. The Apo o4 allele seems to predispose carriers with MS to a faster progression of disease.

Key Words: apo E • genotype • multiple sclerosis • optic neuritis • phenotype • progression rate

Multiple Sclerosis, Vol. 11, No. 5, 511-515 (2005)
DOI: 10.1191/1352458505ms1207oa


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