Apoliprotein E and multiple sclerosis: impact of the epsilon-4 allele on susceptibility, clinical type and progression rate

The purpose of this study was to investigate the relation between APOE genotype and Multiple Sclerosis (MS) in a genetically homogeneous population. We examined 240 patients consulting the MS-clinic during a period of 3 years (1996-1999). The mean age of the patients was 41.7 years (range 19-80 Y, SD 10.0 Y). As a measure of the progression rate (PR) the last registered Expanded Disability Status Scale (EDSS) score was divided by the time span (years) from disease onset until the latest assessment. The APOE genotype was determined from saliva and/or blood samples using PCR-techniques. The prevalence of different APOE genotypes was compared with the allele-distribution in a population of 361 persons from a Danish cross-sectional population study. The frequency of APOE-e4/e4 homozygotes was significantly higher in the MS-group as compared to controls (P<0.05, odds ratio: 2.3), whereas the frequency distribution of other genotypes did not differ significantly. The rate of progression was significantly faster in the APOE-e4/e4 homozygotes compared to other genotypes in the MS group (P<0.05). This study suggests that the APOE-e4/e4 homozygotes have an increased risk of developing MS. MS patients with the APOE-e4/e4 allele may also have an increased rate of disease progression.

[1]  T. Teasdale,et al.  Apolipoprotein E and Subjective Symptomatology Following Brain Injury Rehabilitation , 2000 .

[2]  N. Evangelou,et al.  Association of the APOE ε4 allele with disease activity in multiple sclerosis , 1999, Journal of neurology, neurosurgery, and psychiatry.

[3]  P. Goodfellow,et al.  HLA typing in the United Kingdom multiple sclerosis genome screen , 1998, Neurogenetics.

[4]  J. Haines,et al.  Linkage of the MHC to familial multiple sclerosis suggests genetic heterogeneity. The Multiple Sclerosis Genetics Group. , 1998, Human molecular genetics.

[5]  B. Fontaine,et al.  Apolipoprotein E Polymorphism in Multiple Sclerosis , 1998, Annals of clinical biochemistry.

[6]  M. Daly,et al.  Genomewide scan of multiple sclerosis in Finnish multiplex families. , 1997, American journal of human genetics.

[7]  R. Rosenberg.  Molecular neurogenetics: the genome is settling the issue. , 1997, JAMA.

[8]  M. Carrington,et al.  Chromosome 19 single-locus and multilocus haplotype associations with multiple sclerosis. Evidence of a new susceptibility locus in Caucasian and Chinese patients. , 1997 .

[9]  E. Corder,et al.  Apolipoprotein E Genotype and Rate of Decline in Probable Alzheimer's Disease , 1996 .

[10]  P. Goodfellow,et al.  A genome screen in multiple sclerosis reveals susceptibility loci on chromosome 6p21 and 17q22 , 1996, Nature Genetics.

[11]  G. Lathrop,et al.  Multiple loci for multiple sclerosis , 1996, Nature Genetics.

[12]  J. Haines,et al.  A complete genomic screen for multiple sclerosis underscores a role for the major histocompatability complex , 1996, Nature Genetics.

[13]  D. Hinds,et al.  A full genome search in multiple sclerosis , 1996, Nature Genetics.

[14]  R. Brookmeyer,et al.  Apolipoprotein E genotype and rate of decline in probabole Alzheimer's disease , 1996 .

[15]  R. Brookmeyer,et al.  Apolipoprotein E genotype and rate of decline in probable Alzheimer's disease. , 1996, Archives of neurology.

[16]  B. Weinshenker,et al.  The natural history of multiple sclerosis. , 1995, Neurologic clinics.

[17]  S. Gauthier,et al.  Predictive value of apolipoprotein E genotyping in Alzheimer's disease: Results of an autopsy series and an analysis of several combined studies , 1994, Annals of neurology.

[18]  D. Rubinsztein,et al.  Apo E genotypes in multiple sclerosis, Parkinson's disease, schwannomas and late-onset Alzheimer's disease. , 1994, Molecular and cellular probes.

[19]  J. Fink,et al.  ApoE ϵ4 allelic association with Alzheimer's disease , 1994, Neurology.

[20]  戴 小燕.  Association of apolipoprotein E with sporadic Alzheimer's disease , 1994 .

[21]  João Nicanildo Bastos dos Santos.  Movement of the rhabditiform larva of Strongyloides stercoralis , 1993, The Lancet.

[22]  G. Siest,et al.  Apolipoprotein E-∈A allele and Alzheimer's disease , 1993, The Lancet.

[23]  B. Tycko,et al.  The apolipoprotein ε4 allele in patients with Alzheimer's disease , 1993, Annals of neurology.

[24]  S. Gauthier,et al.  Apolipoprotein E polymorphism and Alzheimer's disease , 1993, The Lancet.

[25]  J. Haines,et al.  Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. , 1993, Science.

[26]  A. D. Roses,et al.  Association of apolipoprotein E allele €4 with late-onset familial and sporadic Alzheimer’s disease , 2006 .

[27]  M. Pericak-Vance,et al.  Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[28]  G. Vogler,et al.  Apolipoprotein E polymorphism in a Danish population compared to findings in 45 other study populations around the world , 1992, Genetic epidemiology.

[29]  PhilipR. Wenham,et al.  Apolipoprotein E genotyping by one-stage PCR , 1991, The Lancet.

[30]  D. Banfield,et al.  Apolipoprotein E genotyping using polymerase chain reaction. , 1990, The New Zealand medical journal.

[31]  B Bass,et al.  The natural history of multiple sclerosis: a geographically based study. 2. Predictive value of the early clinical course. , 1989, Brain : a journal of neurology.

[32]  Shirley A. Miller,et al.  A simple salting out procedure for extracting DNA from human nucleated cells. , 1988, Nucleic acids research.

[33]  N. Rifai,et al.  Changes in cerebrospinal fluid IgG and apolipoprotein E indices in patients with multiple sclerosis during demyelination and remyelination. , 1987, Clinical chemistry.

[34]  J. Kurtzke.  Rating neurologic impairment in multiple sclerosis , 1983, Neurology.

[35]  A. Svejgaard,et al.  Histocompatibility determinants in multiple sclerosis, with special reference to clinical course. , 1973, Lancet.

[36]  V. Shore,et al.  Heterogeneity of human plasma very low density lipoproteins. Separation of species differing in protein components. , 1973, Biochemistry.

[37]  L. Hagerup,et al.  [An investigation of 50-year-old persons in Glostrup in 1964-65]. , 1968, Ugeskrift for laeger.

[38]  Powley Jm.  SYMPTOMLESS CANCER IN WOMEN. , 1964 .