Association between CTLA-4 +49 A/G polymorphism and type 1B diabetes in Japanese population
- 46 Downloads
+49 A/G polymorphism of CTLA-4 gene has been suggested to be associated with type 1 diabetes in some populations. However, a functional significance of the +49 A/G polymorphism is unknown, because it is believed the polymorphism does not affect the function of the CTLA-4 molecule. In this study, we examined the +49 A/G polymorphism of the CTLA-4 gene in 30 Japanese type 1 diabetic patients (14 type 1B and 16 type 1A) and 40 non-diabetic subjects in a case-control study, and stratified patients according to genotype of the polymorphism. The distribution of genotype frequencies differed between type 1 diabetic patients and controls (p<0.01). When the subjects were subdivided into type 1A and type 1B subgroups, a significant difference in G allele frequency was found only between type 1B patients and controls, whereas G allele frequency tended to be higher in type 1A diabetic patients than controls. Type 1B patients displayed more severe metabolic decompensation (higher plasma glucose concentration, lower urinary C-peptide levels, higher insulin requirement, and higher serum amylase levels), and were found to be more prone to diabetic ketoacidosis than type 1A patients. After stratification by genotype, differences in urinary C-peptide and serum amylase levels between type 1A and type 1B patients were found to be due to differences in the GG genotype subgroup, whereas in the AG subgroup those differences disappeared. In conclusion, the +49 A/G polymorphism of CTLA-4 gene was associated with the occurrence of type 1B diabetes in a Japanese population, and type 1B diabetics with a GG genotype were associated with more severe cell dysfunction than their type 1A counterparts.
Key WordsCTLA-4 polymorphism type 1 diabetes type 1B diabetes autoantibody
Unable to display preview. Download preview PDF.
- 7.Abiru, N., Kwasaki, E., and Eguch, K. (2000). Diabetes Metab. Rev. 18, 357–366.Google Scholar
- 8.Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. (1997). Diabetes Care 20, 83–97.Google Scholar
- 16.Yakota, I., Shirakawa, N., Shima, K., et al. (1996). Diabetes Care 19, 74–75.Google Scholar