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 protein tyrosine 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 autoimmunity 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 confers genetic susceptibility to type 1 diabetes, particularly in patients with thyroid autoimmunity.