中文摘要：

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。

英文摘要：

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.