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  • Title: The association of CTLA4 polymorphism with type 1 diabetes is concentrated in patients complicated with autoimmune thyroid disease: a multicenter collaborative study in Japan.
    Author: Ikegami H, Awata T, Kawasaki E, Kobayashi T, Maruyama T, Nakanishi K, Shimada A, Amemiya S, Kawabata Y, Kurihara S, Tanaka S, Kanazawa Y, Mochizuki M, Ogihara T.
    Journal: J Clin Endocrinol Metab; 2006 Mar; 91(3):1087-92. PubMed ID: 16352685.
    Abstract:
    CONTEXT: Transracial studies are a powerful tool for genetic association studies of multifactorial diseases, such as type 1 diabetes. The low incidence of type 1 diabetes in Asian countries, however, makes it difficult to perform large-scale studies in Asia. OBJECTIVE: To overcome this, we have assembled a multicenter study group in Japan and studied the association of CTLA4 polymorphisms with type 1 diabetes relative to autoimmune thyroid disease (AITD) phenotypes. SUBJECTS: Subjects included a total of 1837 samples, including 1114 cases (769 with type 1 diabetes and 345 with AITD) and 723 control subjects. METHODS: The +6230G>A and +49G>A polymorphisms of CTLA4 as well as HLA-DRB1 and -DQB1 were genotyped. RESULTS: The +6230G>A polymorphism was significantly associated with type 1 diabetes complicated with AITD (odds ratio, 1.54; P = 0.027) and with AITD alone (odds ratio, 1.31; P = 0.045) but not with type 1 diabetes without AITD. The association with type 1 diabetes positive for autoantibodies to both pancreatic islets and thyroid was particularly strong (odds ratio, 1.87; P = 0.001). Type 1 diabetic patients with the disease-associated GG genotype were characterized by a significantly higher frequency of AITD (P = 0.013), of positivity for both AITD and antiislet autoantibody (P = 0.00086), and of high-risk HLA genotypes (P = 0.034). CONCLUSIONS: Given the high frequency of AITD in patients with type 1 diabetes, these data suggest the possibility that the association of CTLA4 with type 1 diabetes in previous studies may have been secondary to AITD, suggesting the importance of subclassification of type 1 diabetes relative to AITD in genetic studies.
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