The Role of Interferon Regulatory Factor 5 Gene Polymorphisms in Systemic Lupus Erythematosus
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The Role of Interferon Regulatory Factor 5 Gene Polymorphisms in Systemic Lupus Erythematosus

The Role of Interferon Regulatory Factor 5 Gene Polymorphisms in Systemic Lupus Erythematosus


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This dissertation, "The Role of Interferon Regulatory Factor 5 Gene Polymorphisms in Systemic Lupus Erythematosus" by Ho-on, Siu, 蕭可安, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled The Role of Interferon Regulatory Factor 5 Gene Polymorphisms in Systemic Lupus Erythematosus submitted by Siu Ho On for the Degree of Master of Philosophy at the University of Hong Kong in August 2007 Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by immune dysregulation of T and B cell interaction, leading to the production of auto-antibodies and formation of immune complexes. The level of type I interferon (IFN) is correlated with both disease activity and severity, and is therefore suggested to be involved in the pathogenesis of SLE. The regulation of type I IFN gene can be modulated by a family of transcription factors, including IFN Regulatory Factors (IRFs) 3, 5 and 7. Biologically, IRF5 controls inflammation, immunity and apoptosis. Irf5 knockout mouse shows reduced production of pro-inflammatory cytokines, including IL-6, IL-12 and TNF-α in response to Toll-like receptor (TLR) engagement. Recently several association studies in different populations have reported that IRF5 is a susceptibility gene for SLE. With these evidences, we hypothesized that IRF5 polymorphisms and haplotypes may be associated with susceptibility to as well as the development of clinical symptoms of SLE in Hong Kong Chinese. Four single nucleotide polymorphisms (SNPs), namely rs2004640, rs41298401, rs2070197 and rs10954213, of IRF5 were investigated for their association with SLE in a case-control study. This study included 410 SLE patients and 444 controls. Linkage disequilibrium (LD) analysis between SNPs was performed and haplotype construction was estimated by expectation-maximization. Association of SNPs with clinical features and auto-antibody profile of SLE was also studied. In addition, the correlation between the SNP rs41298401 and IRF5 mRNA expression of exon 1 isoforms and total IRF5 was investigated respectively. The CC genotype and C allele of the SNP rs41298401 were associated with an increased risk of developing SLE (OR 1.638 94% C.I. 1.11-2.43; P=0.028 and OR 1.49 95% C.I. 1.10-2.00; P=0.01, respectively). However, no association with disease susceptibility was found for the functional SNPs rs2004640 and rs10954213. In addition, the SNP rs2070197 was found to be non-polymorphic as confirmed in 190 individuals in our population. Eight haplotypes were constructed in the order of rs2004640, rs41298401 and rs10954213. A significant difference in the distribution of IRF5 haplotypes between patients and controls (P=0.009) was detected. The significant difference was mainly contributed by the risk haplotype T-C-A and protective haplotype G-G-A. We further investigated the functional role of the significantly associated SNP by analyzing their association with mRNA expression. However, similar IRF5 exon 1 isoforms and total mRNA expression was detected in samples with different genotypes of the SNP rs41298401. In conclusion, IRF5 polymorphisms were associated with SLE in Hong Kong Chinese. The genotypes of the polymorphism rs41298401 were not associated with the alternative splicing and transcriptional activities of IRF5. However, an overall difference in the distribution of the haplotype frequencies (rs2004640, rs41298401 and rs10954213) between SLE patients a nd controls was detected. The haplotype T-C-A was identified as a risk haplotype associated with SLE. These findings provide some insi


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Product Details
  • ISBN-13: 9781374665415
  • Publisher: Open Dissertation Press
  • Publisher Imprint: Open Dissertation Press
  • Height: 279 mm
  • No of Pages: 138
  • Weight: 612 gr
  • ISBN-10: 137466541X
  • Publisher Date: 27 Jan 2017
  • Binding: Hardback
  • Language: English
  • Spine Width: 10 mm
  • Width: 216 mm


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