CBLB 基因和小兒自體免疫性甲狀腺疾病-病例對照性研究

Graves' disease, and Hashimoto's thyroiditis are multi-genes complex diseases. The risks of the diseases to siblings and offspring of affected individuals are higher than to general population. The concordance rate between monozygotic twins is greater than that between dizygotic twins. These suggest that genes play some role in the diseases. The presence of autoantibodies and infiltration of both B and T cells in either islets or thyroid indicate autoimmunity. The Komeda diabetes-prone (KDP) rat is a spontaneous animal model of human type 1 diabetes and characterized by autoimmune destruction of pancreatic ?-cells, rapid onset of overt diabetes with no sex difference, and no significant T-cell lymphopenia. Pathological findings also show polyglandular involvement including thyroid gland. Sequence analysis of the cblb cDNA from the KDP rat identified a C→T homozygous nonsense mutation (arginine to a stop at codon 455, Arg455X) that removes 484 amino acids, including the proline-rich region and leucine zipper domain. Thus cblb contributes significantly to the development of type 1 diabetes in the KDP rat. The cblb gene encodes a large protein that has a proline rich domain, a nuclear localization signal, a C3HC4 zinc finger, and a putative leucine zipper. The cblb protein can interact with signal transduction proteins to regulate their function or to be regulated by them. Cblb functions as a negative regulator of autoimmunity. Impairment of the cblb signaling pathway may contribute to human autoimmune diseases. Thus, the gene cblb is a potential candidate for autoimmunity. The defection of Cblb signal transduction pathway will lead to autoimmune disease including Diabetes mellitus type I, Grave’s disease and Hashimoto disease. As a result the CBLB gene is one of the candidate gene in the research of autoimmune mechanism. There are 7 SNP on CBLB gene. Our research points out 4 SNP, which have a rate of allele bigger than 0.20 refer to the NCBI database. We had verified 2 SNP from 4 of it on compatriot’s genes by DNA sequencing. We used the production of PCR, fragment of RFLP to analyze the polymorphism and mutation of cblb gene of 60 patients with Hashimoto disease and 388 controls. On the other hand, we examined the association between cblb gene and disease by Chi-square test and Hardy-Weinberg equilibrium. The result demonstrates that these two SNPs (rs2305035 and rs2305037) do not have significant association with Hashimoto disease. This experiment does not demonstrate the significant association between cblb gene and thyroiditis. As a result, CBLB may not be the clue gene of Hashimoto disease in our compatriot.