Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.628340
Title: Gene polymorphisms in SLE
Author: Guerra, Sandra
Awarding Body: King's College London (University of London)
Current Institution: King's College London (University of London)
Date of Award: 2013
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Abstract:
Systemic lupus erythematosus (SLE) is an autoimmune disease, with a strong genetic component. It is characterised by hyperactive T and B cells, chronic inflammation and the production of antinuclear autoantibodies. SLE affects mostly women of child baring age, with a 9:1 ratio, women to men and has been reported to be more prevalent in people of non-European ancestry. In the era of genome-wide association studies (GWAS), elucidating the genetic factors present in SLE has been very successful, with over 28 confirmed disease susceptibility loci mapped and a number of candidate genes identified. During this thesis I fine mapped IL18 as it had previously been reported to be associated with SLE, SNP rs360719. After fine mapping and subphenotype analysis in UK and African American cohorts, I was unable to replicate the published association. Although genetic data did not confirm IL18 to be associated with SLE, I demonstrated increased IL-18 serum levels in SLE renal patients compared to SLE patients. I further analysed IL10, another previously associated SLE candidate loci in our current SLE GWAS cohort (4000 cases and 9000 controls) of European ancestry. I again was unable to replicate the previous association, however using other SLE GWAS data showed SNP rs3024505 to be associated in Northern European samples. Further analysing our SLE GWAS, I located IKZF3 as a candidate loci. I identified an associated block of 56 SNPS and located the association to a single SNP rs2941509, p=1.46xlQ-8. Furthermore, I demonstrated an allelic imbalance in this SNP, with the protective G allele being expressed 1.5 times greater than the risk A allele, in controls. These data here demonstrated in this thesis indicates the importance of fine mapping candidate loci and verification of previously associated loci. This thesis contributes to the current knowledge of SLE by demonstrating discrepancies in published association data and showing the importance of larger studies.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.628340  DOI: Not available
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