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CTLA-4+49A/G和CT60基因多态性与1型糖尿病合并甲状腺自身免疫的相关性 被引量:11

Association of CTLA-4 + 49A/G and CT60 gene polymorphism with type 1 diabetes and thyroid autoimmunity
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摘要 目的探讨细胞毒性T淋巴细胞相关抗原4(CTLA-4)+49A/G和CT60基因多态性与1型糖尿病(T1DM)合并甲状腺自身免疫的关系。方法对332例T1DM,476名健康对照进行CTLA-4基因多态性及甲状腺自身抗体检测。CTLA-4+49A/G、CT60基因型采用限制性片段长度多态性检测,甲状腺过氧化物酶抗体(TPOAb)、甲状腺球蛋白抗体(TGAb)采用放射免疫法检测,谷氨酸脱羧酶抗体(GADA)、蛋白酪氨酸磷酸酶抗体(IA-2A)采用放射配体法检测。结果(1)T1DM患者中CTLA-4+49A/G基因型GG频率高于健康对照(47.3%比35.1%,OR=1.66,P〈0.01),合并甲状腺自身免疫的T1DM基因型GG频率更高(56.8%,OR=2.43,P〈0.01)。(2)T1DM中CTLA-4CT60基因型GG频率高于健康对照(67.8%比56.7%,OR=1.60,P=0.02),而合并甲状腺自身免疫T1DM患者基因型GG频率更高(77,8%,OR=2.67,P〈0.01)。(3)与甲状腺抗体阴性的T1DM相比,甲状腺抗体阳性的T1DM CTLA-4CT60基因型GG频率更高(77.8%比62.3%,P〈0.05),更易携带谷氨酸脱羧酶抗体(77.8%比57.4%,P〈0.05)。结论CTLA-4+49A/G和CT60基因多态性与T1DM合并甲状腺自身免疫相关。 Objective To investigate the association of CTLA-4 + 49A/G and CT60 gene polymorphisms with type 1 diabetes (T1DM) and thyroid autoimmunity. Subjects Three hundred thirty-two T1DM patients and 476 controls were recruited in the study. Method The CTLA4 + 49 A/G and CT60 polymorphisms of CTLA4 gene were analyzed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. Thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb) were determined by radioimmunoassay. Glutamic acid decarboxylase antibody (GADA) and proteintyrosine phosphatase antibody (IA-2A) were measured by radioligand immunoassay. Results ( 1 ) The CTLA4 + 49 A/G polymorphism was significantly associated with T1DM complicated with thyroid autoimmunity ( OR = 2. 43, P 〈 0. 01 ) and with T1DM alone ( OR = 1.66, P 〈 0. 05 ). (2) The CTLA4 CT60 polymorphism was also significantly associated with T1DM complicated with thyroid autoimmunity (0R=2.67, P 〈0.01) and with T1DM alone (OR = 1.60,P =0.02). (3) T1DM with thyroid autoimmuntiy was characterized by a significantly higher frequency of CTLA-d CT60 GG genotype (77. 8% vs 62. 3%, P 〈0. 05) and GADA (77.8% vs 57.4%, P 〈0. 05) compared to the patients without thyroid antibodies. Conclusion CTLA4 + 49 A/G and CT60 gene polymorphism confers genetic susceptibility to type 1 diabetes, particularly in patients with thyroid autoimmunity.
出处 《中华医学杂志》 CAS CSCD 北大核心 2009年第18期1246-1249,共4页 National Medical Journal of China
基金 国家重点基础研究发展计划基金(2006CB503901) 国家自然科学基金(30670991),湖南省自然科学基金(06JJ2086),长沙市科技局重点基金(K061025-32)
关键词 糖尿病 Ⅰ型 甲状腺炎 自身免疫性 CTLA-4 基因多态性 Diabetes mellitus, type 1 Thyroiditis, autoimmunity Cytotoxic T lymphocyte antigen 4
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