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Preliminary Observations on APOE 4 Allele and Progression of Disability in Multiple Sclerosis

Joab Chapman, MD, PhD; Constanatin Sylantiev, MD; Puiu Nisipeanu, MD; Amos D. Korczyn, MD, MSc

Arch Neurol. 1999;56:1484-1487.

Background  Apolipoprotein E expression is increased in regenerating neural tissue and the APOE 4 allele is associated with impaired neuronal repair. Since repair is essential for the restoration of central nervous system function following multiple sclerosis (MS) relapses, APOE genotype may influence clinical progression of the disease.

Objective  To examine the association of the APOE genotype with disease susceptibility and progression in MS.

Patients and Methods  APOE genotyping was determined by polymerase chain reaction and restriction enzyme digestion in 47 patients with MS who had been followed up every 3 months for 2 years as part of an open-label clinical trial with glatiramer acetate. The Expanded Disability Status Scale (EDSS) was used to assess clinical progression.

Results  Nine patients were heterozygous and 1 patient was homozygous for the APOE 4 allele, for a frequency of 12% (11/94), which is similar to that of the general Israeli population. The APOE 4 carriers had a mean ± SE EDSS score of 3.10 ± 0.45 at entry, which was not significantly different from the remaining 37 patients (2.62 ± 0.25). During the observation period, the EDSS score of the APOE 4 carriers deteriorated to 4.00 ± 0.63 while the other patients remained stable with an EDSS score of 2.74 ± 0.31. The interaction of genotype with disability over time was significant (P = .02 by repeated-measures analysis of variance). There were no differences in the number of relapses occurring in the 2 groups.

Conclusions  These preliminary observations suggest that APOE genotype may influence disease progression in MS. The APOE 4 allele was not associated with an increased risk of MS or relapses.

From the Department of Neurology and Neuroimmunology Clinic, Tel Aviv Medical Center, Tel Aviv, Israel.

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