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This dissertation, Association Between {221}-Chemokine Gene Polymorphisms and Tuberculosis by Sok-fan, Chu, 朱淑芬, 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 between β-Chemokine Gene Polymorphisms and Tuberculosis Submitted by Chu Sok Fan for the Degree of Master of Philosophy at the University of Hong Kong in August 2005 Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (MTB). It has been estimated that one third of the human populations are infected with MTB. TB is a significant public health burden accounting for 8.8 million new cases and 1.7 million deaths worldwide in 2003. Hong Kong is a place of intermediate burden of TB with a notification rate of around 110 per 100,000 persons. Since only 10% of the infected individuals develop clinical disease in their lifetime, host genetic factors may contribute to the interpersonal differences in the outcome of infections. Chemokines are small chemotactic cytokines that mediate the migration of inflammatory cells to form a characteristic histological structure known as granuloma in TB. The genes of β-chemokines, a sub-family of chemokines, are clustered at chromosome 17q11.2 in humans. Family-based genome wide studies have shown the linkage of the β-chemokine locus to susceptibility to TB. This study focused on the three most intensively studied members of β-chemokines, including CCL2 monocyte chemotactic protein-1; MCP-1), CCL3 (macrophage inflammatory protein-1α; MIP-1α), and CCL5 (regulated upon activation, normal T cell expressed and secreted; RANTES), which had been associated with complex diseases. We hypothesized that the genetic polymorphisms regulating the transcription of these genes might contribute to TB susceptibility. Five reported functional single nucleotide polymorphisms (SNPs) in the β-chemokine genes were investigated: MCP-1 -2518 A/G, RANTES -403 G/A, RANTES -28 C/G, RANTES In1.1 T/C, MIP-1α +459 C/T. Five hundred forty-seven patients and four hundred sixty-two controls were genotyped for the SNPs by polymerase chain reaction-restriction fragment length polymorphism and the genotype and allele frequencies were compared between the two groups of subjects. Linkage disequilibrium (LD) between each SNP within the same gene was measured. The frequencies of CCL5 haplotypes were estimated by the expectation-maximization algorithm and those of the combined genotypes of the three CCL5 SNPs were determined for patients with TB and controls. Although we did not find any significant differences in the genotype and allele frequencies of the individual SNPs of the β-chemokine genes between patients and controls, a substantial difference in the LD pattern of SNPs in the CCL5 gene was observed between patients with TB and controls. Furthermore, we found a significant difference in the distribution of CCL5 haplotypes between patients and controls (PDOI: 10.5353/th_b3573613 Subjects: Tuberculosis - Genetic aspectsChemokinesGranulomaGenetic polymorphisms

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