Association of CTLA-4 gene A/G polymorphism in Japanese type 1 diabetic patients with younger age of onset and autoimmune thyroid disease

• Published in: Diabetes care Vol. 23; no. 7; pp. 975 - 978
• Main Authors: TAKARA, M, KOMIYA, I, KINJO, Y, TOMOYOSE, T, YAMASHIRO, S, AKAMINE, H, MASUDA, M, TAKASU, N
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.07.2000
• Subjects: Abatacept; Adolescent; Adult; Age; Age of Onset; Aged; Alanine; Antibodies; Antigens, CD; Antigens, Differentiation - genetics; Asian Continental Ancestry Group - genetics; Autoantibodies - blood; Biological and medical sciences; Child; Comorbidity; CTLA-4 Antigen; Diabetes; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - immunology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Glutamate Decarboxylase - immunology; Graves disease; Humans; Immunoconjugates; Islets of Langerhans - immunology; Isoenzymes - immunology; Japan; Lymphocytes; Male; Medical sciences; Middle Aged; Patients; Peptides; Physiological aspects; Polymerase chain reaction; Polymorphism; Polymorphism, Genetic; Research design; Threonine; Thyroid diseases; Thyroiditis, Autoimmune; Thyroiditis, Autoimmune - genetics; Thyroiditis, Autoimmune - immunology; Type 1 diabetes; Womens health; Japan; Endocrinopathy; Human; Immunopathology; Concomitant disease; Gene; Thyroid diseases; Insulin dependent diabetes; Molecular epidemiology; Autoimmune disease; Genetic determinism; Age; Polymorphism
• ISSN: 0149-5992; 1935-5548
• DOI: 10.2337/diacare.23.7.975

Association of CTLA-4 gene A/G polymorphism in Japanese type 1 diabetic patients with younger age of onset and autoimmune thyroid disease. M Takara , I Komiya , Y Kinjo , T Tomoyose , S Yamashiro , H Akamine , M Masuda and N Takasu Second Department of Internal Medicine, University of the Ryukyus School of Medicine, Nishihara, Okinawa, Japan. Abstract OBJECTIVE: We studied the association between type 1 diabetes with autoimmune thyroid disease (AITD) and A/G allele polymorphism in exon 1 of the CTLA-4 gene in a Japanese population. RESEARCH DESIGN AND METHODS: We studied 74 Japanese type 1 diabetic patients with or without AITD and 107 normal subjects to identify the association between CTLA-4 polymorphism and type 1 diabetes using polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: The frequency of the CTLA-4 G allele differed significantly between the type 1 diabetic patients (61%) and the normal control subjects (48%) (P = 0.016). The difference in the CTLA-4 G allele became greater between patients with a younger age of onset of type 1 diabetes (age at onset <30 years) and the normal control subjects (64% and 48%, respectively). However, the frequency of the CTLA-4 G allele did not differ between type 1 diabetic patients with younger and older age of onset (64% vs. 57%). The G allele frequencies in the patients with younger-onset type 1 diabetes and AITD increased more than in the control patients (P = 0.025). These differences reflected a significant increase in the frequency of G/G genotype--that is, 54% in those with younger-onset type 1 diabetes and AITD, 39% in those without AITD, and 28% in control subjects. CONCLUSIONS: An association was detected between the CTLA-4 gene polymorphism and younger-onset type 1 diabetes with AITD. The G variant was suggested to be genetically linked to AITD-associated type 1 diabetes of younger onset in this apanese population. The defect in these patients presumably lies in a T-cell-mediated autoimmune mechanism.