CTLA4 gene polymorphism correlates with the mode of onset and presence of ICA512 Ab in Japanese type 1 diabetes.

Abstract

Recently, the association of CTLA4 gene polymorphism with type 1 diabetes and AITD has been reported in several populations. CTLA4 was originally reported to regulate T-cell activity and T-B cognate interaction. To investigate the role of CTLA4 in autoimmune diseases, we examined the correlation between CTLA4 gene polymorphism and the clinical characteristics of Japanese patients with type 1 diabetes, including the mode of onset of diabetes and presence of islet-specific autoantibodies (GAD, ICA 512 Ab) in the serum. We studied 111 patients with type 1 diabetes and 445 normal subjects. CTLA4 exon 1 position 49 (A/G: codon 17: Thr/Ala) polymorphism was defined, employing PCR-RFLP. Sixty-three (57%) patients had AITD. The allele frequencies of G and A in both 111 patients (G: 65%; A: 35%) and 63 patients (G: 62%; A: 38%) were not significantly different from the control subjects (G: 63%; A: 37%). Serum samples of 69 patients were obtained within a year after onset and used for pancreas specific autoantibodies analysis. These samples were also used for further analysis between CTLA4 gene polymorphism and clinical characteristics. The allele frequencies of G and A in patients who presented with diabetic ketoacidosis (DK+) (G: 75%; A: 25%) were significantly different from those in DK- patients (G: 50%, A: 50%, P = 0.003). Allele and genotype analyses showed significant differences between DK+ patients and control subjects (P = 0.014, P = 0.046, respectively). Allele frequencies of G and A were not significant between patients who were positive and negative for GAD Ab, but significant for ICA 512 Ab (G: 83%, A:17% versus G: 59%, A: 41%: positive patients versus negative patients, P = 0.004). Our results showed a significant correlation between CTLA4 gene polymorphism and ICA 512 Ab. Our results also indicated that CTLA4 gene polymorphism is associated with the onset mode of Japanese type 1 diabetes and the presence of ICA512 Ab. Further analysis of this polymorphism is necessary to fully understand the pathogenesis and progression of type 1 diabetes.

• Authors: T Abe, H Takino, H Yamasaki, M Ozaki, Y Sera, H Kondo, H Sakamaki, E Kawasaki, T Awata, Y Yamaguchi, K Eguchi
• Journal: Diabetes research and clinical practice (Diabetes Res Clin Pract) Vol. 46 Issue 2 Pg. 169-75 (Nov 1999) ISSN: 0168-8227 [Print] Ireland
• PMID: 10724097 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• Antigens, Differentiation
• Autoantibodies
• Autoantigens
• CTLA-4 Antigen
• CTLA4 protein, human
• Immunoconjugates
• Membrane Proteins
• Abatacept
• PTPRN protein, human
• Protein Tyrosine Phosphatase, Non-Receptor Type 1
• Protein Tyrosine Phosphatases
• Receptor-Like Protein Tyrosine Phosphatases, Class 8

Topics

• Abatacept
• Adolescent
• Adult
• Aged
• Antigens, CD
• Antigens, Differentiation (genetics)
• Asian People (genetics)
• Autoantibodies (analysis)
• Autoantigens
• Autoimmune Diseases (complications)
• CTLA-4 Antigen
• Child
• Child, Preschool
• Diabetes Mellitus, Type 1 (complications, ethnology, genetics, immunology)
• Humans
• Immunoconjugates
• Infant
• Islets of Langerhans (immunology)
• Japan
• Ketosis (complications)
• Membrane Proteins (immunology)
• Middle Aged
• Polymorphism, Genetic
• Protein Tyrosine Phosphatase, Non-Receptor Type 1
• Protein Tyrosine Phosphatases (immunology)
• Receptor-Like Protein Tyrosine Phosphatases, Class 8
• Reference Values
• Thyroid Diseases (complications)