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Title: The relationship of genetic polymorphisms to disease severity of multiple sclerosis.
Author: Mann, C. L. A.
Awarding Body: University of Keele
Current Institution: Keele University
Date of Award: 2000
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The glutathione S-transferase (GST) supergene family encodes isoenzymes that appear to be critical in protection against oxidative stress. Certain GST loci are polymorphic, demonstrating alleles that are null (GSTMI/GSTT1), encode low activity variants (GSTPI), or are associated with variable inducibility (GSTM3). Interleukin-1 (IL- 1) alpha and beta are cytokines involved in recruitment of inflammatory cells, the process of inflammation, and blood-brain barrier breakdown and nerve regeneration. Polymorphisms of both GST and of a complementary interleukin-1 receptor antagonist have been associated with severity and susceptibility to other inflammatory conditions. This thesis examines the influence of the GST and IL-1 genes on both the susceptibility to Multiple Sclerosis (MS), and the course of disease progression. The population examined consisted of four hundred patients with clinically definite MS. Disease severity was measured using the Kurtzke Expanded Disability Status Scale (EDSS), a robust established ranking scale. PCR-based genotyping was performed using DNA extracted from lymphocytes. Significant associations between genotypes and clinical outcome were corrected for known demographic factors influencing prognosis, these being; gender, onset age, and disease duration using the statistical method of logistic regression. Significant associations, withstanding multiple testing corrections, with certain IL-I genotypes and disease severity were found. There was also a significant trend with the GST isoenzymeM 3 that is expressedin nervous tissue. No robust findings suggest that these genes influence susceptibility to MS, but the results suggest that long-term prognosis is genetically influenced by the modulation of inflammatory cytokines and also by the ability to remove the toxic products of oxidative stress.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Disability; MS; Genotypes; Immunopathogenesis Medicine Molecular biology Cytology Genetics