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Association of B Lymphocyte Stimulator (Blys) Polymorphisms with Systemic Lupus Erythematosus (Sle)



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Association of B Lymphocyte Stimulator (Blys) Polymorphisms with Systemic Lupus Erythematosus (Sle) by Man-Wai Ng
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This dissertation, "Association of B Lymphocyte Stimulator (BLyS) Polymorphisms With Systemic Lupus Erythematosus (SLE)" by Man-wai, Ng, 吳雯慧, 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 Association of B Lymphocyte Stimulator (BLyS) polymorphisms with Systemic Lupus Erythematosus (SLE) submitted by Ng Man Wai for the Degree of Master of Philosophy at the University of Hong Kong in August 2005 B lymphocyte stimulator (BLyS) is essential for B cell survival, differentiation, stable germinal centre formation and proper isotype switching. Several lines of evidence suggest that BLyS is a candidate gene of systemic lupus erythematosus (SLE). First, it maps at chromosome 13q34, which is a susceptibility locus of SLE. Second, higher BLyS level is found in lupus mouse models and transgenic mice with BLyS overexpression develop lupus-like symptoms including anti-DNA antibodies and glomerulonephritis. Addition of BLyS antagonists inhibited the development of proteinuria and prolonged the survival of these mice. Finally, higher BLyS level is found in SLE patients and is correlated with anti-dsDNA antibody titers. With this evidence, we hypothesized that BLyS gene polymorphisms and haplotypes may be associated with susceptibility to as well as clinical symptoms development of SLE in Hong Kong Chinese population. A case-control association study of four promoter single nucleotide polymorphisms i (SNPs), -1283G/A, -871C/T, -514T/C, -353G/C, and one intronic SNP, IVS1-45C/G of BLyS were analyzed in 472 SLE patients and 789 controls by high-throughput Sequenom Assay. Association of alleles and genotypes with disease susceptibility, haplotypes construction and linkage disequilibrium (LD) analysis were performed. In addition, association of SNPs with various clinical features and autoantibody profiles, and correlation of SNPs with circulating BLyS level were performed. We found that the GG genotype of the SNP BLyS IVS1-45C/G was associated with increased risk of developing SLE (OR 5.26; 95% CI 1.16-23.8; P = 0.03). However, no association with disease susceptibility was found for BLyS -1283G/A, BLyS -871C/T, BLyS -514T/C, BLyS -353G/C. Three common haplotypes were identified using these five SNP, but similar haplotype frequencies were found between SLE patients and controls. In addition, BLyS -871 CC genotype was associated with higher risk for developing oral ulcers (OR 4.80; 95% CI 1.67-13.8; P = 0.0049) and anti-nRNP autoantibody (OR 2.47; 95% CI 1.38-4.42; P = 0.0017) in SLE patients. We also observed significant difference for the circulating BLyS level in relation to different genotypes of BLyS -871C/T and BLyS IVS1-45C/G. The BLyS -871CC showed higher circulating BLyS level than BLyS -871T/- (P = 0.0052), while BLyS IVS1-45G/- showed higher level when compared to BLyS IVS1-45CC (P = 0.0312). We concluded that BLyS polymorphisms were associated with SLE, with higher circulating BLyS-producing BLyS IVS1-45GG as risk factor of disease development, and BLyS -871CC for developing oral ulcers and anti-nRNP antibody among SLE patients in our population. ii DOI: 10.5353/th_b3205302 Subjects: B cellsSystemic lupus erythematosus - Genetic aspectsCytogenetics
Release date NZ
January 26th, 2017
Created by
colour illustrations
Country of Publication
United States
Open Dissertation Press
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