The association of CTLA4 polymorphism with type 1 diabetes is concentrated in patients complicated with autoimmune thyroid disease:: A multicenter collaborative study in Japan
The association of CTLA4 polymorphism with type 1 diabetes is concentrated in patients complicated with autoimmune thyroid disease:: A multicenter collaborative study in Japan
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DOI：
10.1210/jc.2005-1407
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发表时间：
2006-03-01
影响因子：
5.8
通讯作者：
Ogihara, T
中科院分区：
文献类型：
--
作者：
Ikegami, H;Awata, T;Ogihara, T
背景：跨种族研究是多因素疾病（如1型糖尿病）遗传关联研究的有力工具。然而，亚洲国家的1型糖尿病发病率较低，这使得在亚洲进行大规模研究变得困难。为了克服这一问题，我们在日本组建了一个多中心研究小组，研究了CTLA4多态性与自身免疫性甲状腺疾病（AITD）表型相关的1型糖尿病的关系。研究对象：共纳入1837份样本，其中1114例（1型糖尿病769例，AITD 345例）和723例对照。方法：对CTLA4 +6230G>A和+49G>A多态性以及HLA-DRB1和-DQB1进行基因分型。结果：+6230G>A多态性与1型糖尿病合并AITD（优势比，1.54,P = 0.027）和单独AITD（优势比，1.31,P = 0.045）相关，但与不合并AITD的1型糖尿病无关。胰岛和甲状腺自身抗体阳性与1型糖尿病的相关性特别强（优势比，1.87;P = 0.001）。伴有疾病相关GG基因型的1型糖尿病患者AITD （P = 0.013）、AITD和抗胰岛自身抗体均阳性（P = 0.00086）、HLA高危基因型（P = 0.034）的发生率显著高于糖尿病患者。结论：考虑到AITD在1型糖尿病患者中的高发生率，这些数据提示CTLA4与1型糖尿病的关联可能是继发于AITD的，提示1型糖尿病相对于AITD的亚分类在遗传学研究中的重要性。
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.