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.
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 diabeticpatients 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.
Authors: Maria Justina B Villano; Amanda K Huber; David A Greenberg; Brian K Golden; Erlinda Concepcion; Yaron Tomer Journal: J Clin Endocrinol Metab Date: 2009-01-13 Impact factor: 5.958
Authors: Oindrila Raha; Subhankar Chowdhury; Samir Dasgupta; P Raychaudhuri; B N Sarkar; P Veer Raju; V R Rao Journal: Int J Diabetes Dev Ctries Date: 2009-04
Authors: Helen Gogas; Urania Dafni; Henry Koon; Maria Spyropoulou-Vlachou; Yannis Metaxas; Elizabeth Buchbinder; Eirini Pectasides; Dimosthenis Tsoutsos; Aristidis Polyzos; Alexandros Stratigos; Christos Markopoulos; Petros Panagiotou; George Fountzilas; Ourania Castana; Pantelis Skarlos; Michael B Atkins; John M Kirkwood Journal: J Transl Med Date: 2010-11-03 Impact factor: 5.531