CTLA4 gene polymorphism correlates with the mode of onset and presence of ICA512 Ab in Japanese Type 1 diabetes
| Autor: | Takahiro Abe, Hiroyuki Sakamaki, Hironori Yamasaki, Hideaki Kondo, Yasunori Sera, Masako Ozaki, Takuya Awata, Hirofumi Takino, Eiji Kawasaki, Katsumi Eguchi, Yoshihiko Yamaguchi |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Adult
medicine.medical_specialty Immunoconjugates Adolescent Diabetic ketoacidosis Endocrinology Diabetes and Metabolism Autoantigens Genetic determinism Autoimmune Diseases Abatacept Islets of Langerhans Endocrinology Asian People Japan Antigens CD Reference Values Diabetes mellitus Internal medicine Genotype Internal Medicine Humans Medicine CTLA-4 Antigen Receptor-Like Protein Tyrosine Phosphatases Class 8 Allele Child Allele frequency Aged Autoantibodies Protein Tyrosine Phosphatase Non-Receptor Type 1 Type 1 diabetes Polymorphism Genetic business.industry Autoantibody Infant Membrane Proteins Ketosis General Medicine Middle Aged medicine.disease Antigens Differentiation Thyroid Diseases Diabetes Mellitus Type 1 Child Preschool Protein Tyrosine Phosphatases business |
| Zdroj: | Diabetes Research and Clinical Practice. 46:169-175 |
| ISSN: | 0168-8227 |
| DOI: | 10.1016/s0168-8227(99)00084-4 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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