Association of CTLA-4 polymorphism with positive anti-GAD antibody in Japanese subjects with type 1 diabetes mellitus

Citation
H. Hayashi et al., Association of CTLA-4 polymorphism with positive anti-GAD antibody in Japanese subjects with type 1 diabetes mellitus, CLIN ENDOCR, 51(6), 1999, pp. 793-799
Citations number
31
Categorie Soggetti
Endocrynology, Metabolism & Nutrition","Endocrinology, Nutrition & Metabolism
Journal title
CLINICAL ENDOCRINOLOGY
ISSN journal
03000664 → ACNP
Volume
51
Issue
6
Year of publication
1999
Pages
793 - 799
Database
ISI
SICI code
0300-0664(199912)51:6<793:AOCPWP>2.0.ZU;2-T
Abstract
OBJECTIVE CTLA-4, expressed on activated T cells, is thought to be a negati ve regulator of T cell function. Its gene (2q33) may confer genetic suscept ibility to type 1 diabetes mellitus (IDDM12), The present study was underta ken to clarify the role of CTLA-4 gene polymorphism in Japanese subjects wi th type 1 diabetes and its effect on their clinical features. SUBJECTS AND METHODS In 117 Japanese subjects with type 1 diabetes, the CTL A-4 exon 1 polymorphism (49 A/G) was defined by PCR-RFLP analysis. Anti-GAD antibodies (GAD-Ab) and fasting serum C-peptide were also determined. 141 healthy age-and sex-matched subjects served as controls. RESULTS The frequency of each polymorphism was not different between the ty pe 1 diabetic subjects and the controls; AA 21, AG 42 and GG 54 for the dia betic subjects, and AA 22, AG 47 and GG 72 for the controls. The frequency of the GG genotype was higher in the diabetic subjects with positive GAD-Ab (greater than 8 U/ml) (67%) than in the GAD-Ab negative subjects (39%) (P < 0.05). The prevalence of positive GAD-Ab declined with the duration of di abetes. In the diabetic subjects with disease duration of less than 5 years (n = 40), the frequency of the GG genotype was also higher in the GAD-Ab p ositive subjects (71%) (P < 0.05). In the analysis of all the diabetic subj ects, there was a strong association between positive GAD-Ab (P < 0.0001). CONCLUSIONS There was no evidence that the CTLA-4 exon 1 polymorphism (49 A /G) confers genetic susceptibility to type 1 diabetes mellitus in our case- control study in Japanese subjects. However, the frequency of positive GAD- Ab was higher in the GG subjects. CTLA-4 polymorphism might contribute to t he clinical heterogeneity of type 1 diabetes mellitus in Japanese subjects.