Genetic Polymorphisms in Graves’ Disease Patients

• Main Authors: Rong-Hsing Chen, 陳榮興
• Other Authors: Fuu-Jen Tsai
• Format: Others
• Language: zh-TW
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/81524587261688096789

碩士 === 中國醫藥大學 === 醫學研究所 === 92 === Graves’ disease (GD) is a common autoimmune thyroid disease. Its pathogenesis involves the production of thyrotropin receptor antibody (TRAb) through a cascade of immune reactions. The presentation of cytosolic peptide antigen with HLA molecule at the cellular surface and the activities of cytokines participate in these procedures. Interleukin-1 (IL-1), IL-6 and tumor necrosis factor-α (TNF-α) not only are proinflammatory cytokines, but also have immunoregulatory activities; on the other hand, transporter associated with antigen processing (TAP) is responsible for cytosolic peptide transport and contributes to the presentation of endogenous antigen with HLA molecule. The aim of this study, therefore, investigates the relationship between the nucleotide variations in genes encoding cytokines and TAP and the susceptibility to GD. Single nucleotide polymorphisms (SNPs) are useful in identification of associated genes with complex diseases. An alteration of a single nucleotide in a gene may interfere with the gene expression and protein production, and consequently, the susceptibility to disease. The study of genetic correlation with GD using SNPs analysis has been undergoing, but, however, is not complete. Further search of candidate genes for GD is necessary. Thus, this study screened the position polymorphisms of IL-1β gene promoter (－350), IL-1β gene exon 5, IL-1 receptor antagonist (IL-1Ra) gene intron 2, IL-6 gene promoter (－572), TNF-α gene promoter (－308) and TAP1 gene condons 333 and 637. Polymerase chain reaction (PCR)-based restriction analyses were used in this study. The results demonstrated positive correlation between CC homozygous genotype/C allele in IL-1β gene promoter (odds ratios: 2.558 and 1.589, respectively) and AG heterozygous genotype/G allele in TAP1 gene codon 637 (odds ratio: 2.745 for G allele) with the susceptibility to GD. However, there were no statistical difference in polymorphisms of IL-1β gene exon 5, IL-1Ra gene intron 2, IL-6 gene promoter, TNF-α gene promoter and TAP1 gene codon 333 between GD patients and normal controls. Although positive association does not necessarily imply that carrying the genes will develop clinical disease, it worth to be further studied for the interaction of genes and some risk factors. Documenting gene-environmental interactions may identify groups at highest risk for the development of GD. Thus, it is helpful to understand the candidate genes through studies of genetic polymorphisms. As cytokines are a large group of proteins and the association between the TAP and the susceptibility to GD is still unclear, further study is necessary to understand the genetic predisposition to GD.