Article

APOE genotype is a major predictor of long-term progression of disability in MS

Department of Neurology, Sackler Faculty of Medicine, Tel Aviv Medical Center, Israel.
Neurology (Impact Factor: 8.3). 03/2001; 56(3):312-6. DOI: 10.1212/WNL.56.3.312
Source: PubMed

ABSTRACT The authors recently reported that the APOE epsilon4 allele is associated with significantly greater progression of disability in a 2-year follow-up of patients with MS. In this study, these findings are substantiated and extended in a much larger group of patients followed for up to 40 years.
Two hundred five patients with clinically definite MS who were genotyped for the APOE epsilon4 carrier state were included. Groups of patients with (n = 41) and without (n = 164) APOE epsilon4 alleles were compared for latency to expanded disability status scale (EDSS) scores of 4.0 and 6.0 by Kaplan-Meier analysis with the log rank test. The results were adjusted for age at onset and sex by Cox regression analysis.
The APOE epsilon4 allele frequency in patients with MS (0.10) was similar to that in the general Israeli population. There was a significant effect of APOE genotype on the latency to reach EDSS 4.0 and 6.0 (p = 0.0002 and p = 0.0006 by two-tailed log rank test). Median latencies were shorter by 12 and 11 years in the APOE epsilon4 group for these outcomes. These results were significant after adjustment for age at onset and sex.
The APOE epsilon4 allele is associated with significantly faster progression of disability in MS. This is the first genetic factor to be identified with a major impact on the progression of disability in this disease.

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    • "The study from Sardinia showed that the APOE-ε4 allele increases the risk of PPMS, but only in women [27] whereas the study from The Netherlands did not confirm any such association [44]. A recent study revealed that African Americans female MS patients with APOE-ε4 had an earlier age of onset than Caucasian female MS patients [45], also Albeit Chapman et al. found an earlier age of onset in the APOE- ε4 carriers [26]. Most of other studies as well failed to find such positive association [29–31,33,35,37–39,41]. "
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    • "Sensorimotor function was evaluated by scoring the vibrissae mediated forelimb placing reaction (Hoane et al., 2000; Hoane and Barth, 2001; Schallert and Woodlee, 2005; Barbre and Hoane, 2006). Each rat was held by the trunk ensuring the forelimbs were free to move. "
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    • "It has been evidenced that apoE is involved in the autoimmune diseases. For example, the apoE e4 allele is associated with a progression of disability in MS (Chapman et al., 2001). ApoE deficiency exacerbated experimental allergic encephalomyelitis (EAE), an animal mode for MS, and EAN, as well as increased antigen specific T cell proliferation in both EAE and EAN (Karussis et al., 2003; Yu et al., 2004). "
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