| Budget Amount *help |
¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2001: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2000: ¥500,000 (Direct Cost: ¥500,000)
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| Research Abstract |
Type 1 diabetes mellitus and Graves' disease are autoimmune disorders in which a number of genetic and environmental factors are believed to contribute to the etiology. We have demonstrated the association of HLA class II genotype and CTLA-4 (cytotoxic T lymphocyte antigen 4) gene polymorphism with childhood-onset type 1 diabetes and Graves' disease in Japanese.
The gene responsible for autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) has been cloned and designated the autoimmune regulator gene (AIRE). The AIRE-1 gene is widely expressed in lymphoid tissues including thymus, lymph node, and spleen, as well as in the adrenal cortex and thyroid. AIRE-1 protein is supposed to be a transcription reguratory protein and have a role in the maintenance of immunological tolerance. The aim of this study was to determine whether AIRE-1 gene mutations have any association with childhood-onset type 1 diabetes and Graves' disease in Japanese.
We investigated the presence of the K83E mutation in exon 2 and the R257X mutation in exon 6 in 46 type 1 diabetes children (29 females and 17 males ; age at onset, 0.5-16 years) and 44 Graves' disease children (34 females and 10 males ; age at onset, 3-16 years). The alleles were defined by polymerase chain reaction of genomic DNA and rertriction fragment-length polymorphism analysis (PCR-RFLP) using endonuclease Taq1.HLA class II (DRB1, DQB1) and A/G transition polymorphism of CTLA-4 exon 1 position 49 have been analyzed m those patients.
In this study, no patients with type 1 diabetes and Graves' disease were found to carry the K83E mutation and the R257X mutation.
We conclude, therefore, that the K83E and the R257X mutation in the AIRE-1 gene is not a susceptibility locus for the more common endocrinopathies, type 1 diabetes mellitus and Graves' disease in Japanese children.
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