Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.486179
Title: Genetics and pharmacogenomics of Multiple Sclerosis
Author: O'Doherty , Catherine
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2007
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Abstract:
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system which is th9ught to be triggered by environmental factors in a genetically predisposed individual. The genetic component is probably attributable to the collective effects of a number of genes each conferring a minor risk. One aspect of this project was to identify variations in candidate genes beyond the MHC Class II region which may influence susceptibility to MS. The genes investigated included PACAP, ITGA-I. MHC2TA, IURA and a group of cytokine genes. PACAP and IL7RA were not major MS susceptibility loci. A SNP in ITGA4 showed evidence of a susceptibility effect in two populations, and MHC2TA may influence risk of chronic inflammatory diseases including MS, RA, and JIA. In the screen of cytokine genes an IL23R SNP showed a similar trend in allele frequency between MS patients and controls in two populations. IFN-P is the most prominent disease modifying drug used in the treatment of MS, decreasing relapse rates and delaying progression of the disease. However an estimated 30-50% of patients fail to respond to treatment. The second aim of this project was to detemline polymorphisms which may modify IFN responsiveness. We screened 61 SNPs in 34 candidate response genes, selected on the basis of their function and the literature. We primarily chose SNPs in the promoter region, hypothesizing that polymorphisms may modify 1FN inducibility. Polymorphisms were typed in samples from 255 Irish patients classified as responders or non-responders. A cohort of 120 healthy controls was also included in the study to determine whether these SNPs' influenced susceptibility to MS. We explored allelic combinations which may influence susceptibility to disease and also response to treatment. A JAK2-IL-IOC4SP3 combination most significantly affected'treatment response and a JAK2-ILI O-CASP I0 combination was the most influential in terms of risk modification.
Supervisor: Not available Sponsor: Not available
Qualification Name: Queen's University Belfast, 2007 Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.486179  DOI: Not available
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