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
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.