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Polymorphisms of apolipoprotein E; outcome and susceptibility in multiple sclerosis

Centre for Molecular and Cell Medicine, Postgraduate Medical School, Keele University, Royal Infirmary, Stoke-on-Trent, UK

C LA Mann

Centre for Molecular and Cell Medicine, Postgraduate Medical School, Keele University, Royal Infirmary, Stoke-on-Trent, UK

M B Davies

Centre for Molecular and Cell Medicine, Postgraduate Medical School, Keele University, Royal Infirmary, Stoke-on-Trent, UK

D Carthy

AR.C. Epidemiology Research Unit, University Medical School, Manchester, UK

A A Fryer

Centre for Molecular and Cell Medicine, Postgraduate Medical School, Keele University, Royal Infirmary, Stoke-on-Trent, UK

M D Boggild

Walton Centre for Neurology and Neurosurgery, Liverpool, UK

C Young

Walton Centre for Neurology and Neurosurgery, Liverpool, UK

R C Strange

Centre for Molecular and Cell Medicine, Postgraduate Medical School, Keele University, Royal Infirmary, Stoke-on-Trent, UK

W Ollier

AR.C. Epidemiology Research Unit, University Medical School, Manchester, UK

C P Hawkins

Centre for Molecular and Cell Medicine, Postgraduate Medical School, Keele University, Royal Infirmary, Stoke-on-Trent, UK

Allelic variants of the apolipoprotein E (APOE) gene influence the course of several neurological diseases. In multiple sclerosis the concentration of APOE in cerebrospinal fluid and its intrathecal synthesis is reduced. Specific isoforms of APOE may also be important and it has been suggested that possession of the e4 allele may be associated with a more aggressive disease process. These data prompted us to re-examine, in a large group of patients with multiple sclerosis, the proposal that allelism in the apolipoprotein gene influences disease course. Genotypes were determined in a well-defined group of 370 unrelated Caucasians with clinically definite multiple sclerosis and in 159 healthy controls. Age at onset, sex, disease duration, disease subtype were recorded. Disability was measured using the Kurtzke expanded disability status score in patients with a disease duration of 10 years or greater. There was no significant difference in APOE allele or genotype frequencies between patients and controls, between disease subtypes or between genders. APOE genotype did not significantly influence age of onset, and no significant relationship between genotype, allele frequency and disease severity was found. This study suggests that individual APOE alleles or genotypes do not determine disease susceptibility or the clinical course of multiple sclerosis.

Key Words: multiple sclerosis • apolipoprotein E • polymorphisms • disability • susceptibility

Multiple Sclerosis, Vol. 6, No. 1, 32-36 (2000)
DOI: 10.1177/135245850000600107


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