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This dissertation, Association of PD-1 Gene Polymorphisms With Systemic Lupus Erythematosus by Kai-pang, Kong, 江啟鵬, 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 PD-1 gene polymorphisms with systemic lupus erythematosus submitted by Kong Kai Pang for the Degree of Master of Philosophy at the University of Hong Kong in December 2004 Programmed death 1 (PD-1) is a negative regulator of T-cells and different lines of evidence suggest that PD-1 is a candidate gene in systemic lupus erythematosus (SLE) susceptibility. First, it maps at chromosomal region 2q37.3, which is a susceptibility locus (SLEB2) of SLE. Second, dysregulated PD-1 expression is associated with break of tolerance, through failure to induce inhibitory signal during T- and B-cells activation, -/- which is one of the major steps in developing autoimmunity. Third, PD-1 mice develop lupus-like syndrome. Finally, PD-1 polymorphisms are associated with various autoimmune diseases. The aim of this study is to investigate the association of the PD-1 polymorphisms and haplotypes with systemic lupus erythematosus (SLE) in Hong Kong Chinese population. We performed a case-control association study of 3 single nucleotide polymorphisms (SNPs), PD1.1 G/A, PD1.3 G/A and PD1.5 C/T with SLE. The study included 514 SLE patients and 647 healthy controls. Association of genotypes and alleles with disease, haplotypes construction and linkage disequilibrium (LD) analysis were performed. Association between SNPs and disease phenotypes was also examined. And correlation between various SNPs and PD-1 mRNA expression was investigated. We found the AA genotype and A allele of the SNP PD1.1 were associated with a decreased risk in developing SLE (OR 0.5; P = 0.014 and OR = 0.71; P = 0.007, respectively). However, no association for SNP PD1.5 was found in SLE and SNP PD1.3 was non-polymorphic in our population. As PD1.3 is non-polymorphic in our populations, only four haplotypes were constructed from PD1.1 and PD1.5. No significant difference in haplotypes frequencies was found between SLE patients and controls. However, the frequency of A/C homozygote (i.e. having PD1.1 AA and PD1.5 CC) was reduced in patients than in controls (OR 0.69; P = 0.021). In addition, the SNP PD1.1 was associated with patients showing double positive in anti-Ro and anti-La autoantibodies (OR = 8.03; P = 0.0002). We also observed a significant difference in PD-1 mRNA expression levels among the various genotypes of PD1.1 and PD1.5. The PD1.1 AA showed the lowest expression levels when compared to PD1.1 GA (P = 0.029) and PD1.1 GG (P DOI: 10.5353/th_b3052066 Subjects: ApoptosisGenetic polymorphismsSystemic lupus erythematosusT cells

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