Chapman, J. et al. APOE genotype is a major predictor of long-term progression of disability in MS. Neurology 56, 312-316

Department of Neurology, Sackler Faculty of Medicine, Tel Aviv Medical Center, Israel.
Neurology (Impact Factor: 8.29). 03/2001; 56(3):312-6. DOI: 10.1212/WNL.56.3.312
Source: PubMed


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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    ABSTRACT: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder of the central nervous system. Evidences linking apolipoprotein E (APOE) to myelin repair, neuronal plasticity, and cerebral inflammatory processes suggest that it may be relevant in MS. The main goal of this study was to determine whether the APOE genotypes and alleles are associated with MS patients. In total, 147 MS cases and 168 control subjects from Iranian population were genotyped for APOE gene using PCR-RFLP method. The frequency of APOE-ε2ε3 genotype was significantly higher in controls than cases (14.3% vs. 6.1%, P=0.009, OR=0.39) whereas APOE-ε3ε4 genotype frequency was significantly higher in cases compared with controls (8.2% vs. 3.6%, P=0.03, OR=2.4). APOE-ε2 allele frequency in cases was significantly lower than that of controls (4.4% vs. 8.0%, P=0.03, OR=0.52). Also male controls were significantly more likely to have APOE-ε2 allele (7.8% vs. 1%, P=0.01, OR=0.11). APOE-ε4 allele frequency in cases was significantly higher than control group (4.8% versus 2.1%, P=0.03, OR=2.35). It seems that individuals carrying APOE-ε4 allele and/or APOE-ε3ε4 genotype develop MS two times more than non-carriers. Also APOE-ε2ε3 genotype or APOE-ε2 allele may have a protective role against MS development in Iranian population. Further investigation would be warranted to understand the role of APOE alleles and genotypes and risk of MS.
    Journal of the neurological sciences 06/2012; 320(1-2):22-5. DOI:10.1016/j.jns.2012.05.050 · 2.47 Impact Factor
    • "According to a study by Michikawa et al., promotion of lipid efflux from cultured astrocytes and neurons depends on genotypic properties of ApoE alleles.16 Many studies have shown that +E4 patients have a greater risk for developing CNS disabilities,1718 earlier onset of the disease, more frequent relapses,10 and poorer recovery following relapses9 compared to - E4 patients. ApoE polymorphism is also an important risk factor in development and progression of Alzheimer's disease.7 "
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    ABSTRACT: Apolipoprotein E (ApoE) gene encodes an important protein in reforming injuries of central nervous system (CNS). It is assumed that various ApoE alleles may be functionally different. The purpose of this study was to investigate the distribution of ApoE genotypes in multiple sclerosis (MS) patients in a small cohort of Iranians. In this case-control study, blood samples of patients and healthy volunteers were collected (n = 40) from Neurology Clinic of Alzahra Medical Complex. The ApoE genotypes were determined using DNA extracted from the samples by polymerase chain reaction (PCR) techniques followed by digestion with HhaI restriction enzyme. The results were adjusted for age of MS onset, sex, expanded disability status scale (EDSS), and type of MS (primary or secondary progressive). Results were statistically analyzed using chi-square test. The ApoE3/E3 genotype was detected in the majority of MS patients and the control group. Frequency distribution of E4 allele did not differ significantly between the two groups. There was no difference between ApoE allele and age of disease onset, sex, expanded disability status, or type of multiple sclerosis. We found no significant differences in genotype frequency between patients with multiple sclerosis and the control group. Despite the fact that small sample size was a limitation for our study, it seems that ApoE polymorphism may not be useful as a marker for screening patients with multiple sclerosis.
    Journal of research in medical sciences 12/2011; 16(12):1519-24. · 0.65 Impact Factor
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    • "A recent study reported that African Americans female MS patients who were APOE ε4 carriers had an earlier age of onset than Caucasian female MS patients, indicating that APOE ε allele might not be the independent factor to determine the age of onset in MS [90]. Albeit Chapman et al. found an earlier age of onset in the APOE ε4 carriers [91], most of others failed to find such positive associations [53, 68, 92–94]. "
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    ABSTRACT: Apolipoprotein E (apoE) is a 34.2 kDa glycoprotein characterized by its wide tissue distribution and multiple functions. The nonlipid-related properties of apoE include modulating inflammation and oxidation, suppressing T cell proliferation, regulating macrophage functions, and facilitating lipid antigen presentation by CD1 molecules to natural killer T (NKT) cells, and so forth. Increasing studies have revealed that APOE epsilon allele might be associated with multiple sclerosis (MS), although evidence is still not sufficient enough. In this review, we summarized the current progress of the immunomodulatory functions of apoE, with special focus on the association of APOE epsilon allele with the clinical features of MS and of its animal model experimental autoimmune encephalomyelitis (EAE).
    Clinical and Developmental Immunology 05/2010; 2010(1740-2522):186813. DOI:10.1155/2010/186813 · 2.93 Impact Factor
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