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

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 CTLA-4 + 49 A/G and CT60 polymorphisms of CTLA-4 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 CTLA-4 + 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 CTLA-4 CT60 polymorphism was also significantly associated with T1DM complicated with thyroid autoimmunity (OR=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-4 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 CTLA-4 + 49 A/G and CT60 gene polymorphism coders genetic susceptibility to type 1 diabetes,particularly in patients with thyroid autoimmunity.%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-4 CT60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.