CTLA4 gene polymorphism correlates with the mode of onset and presence of ICA512 Ab in Japanese type 1 diabetes.
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.
Abe
T
T
The First Department of Internal Medicine, Nagasaki University, School of Medicine, Japan.
Takino
H
H
Yamasaki
H
H
Ozaki
M
M
Sera
Y
Y
Kondo
H
H
Sakamaki
H
H
Kawasaki
E
E
Awata
T
T
Yamaguchi
Y
Y
Eguchi
K
K
D000069594:Abatacept; D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D001323:Autoantibodies / Q000032:analysis*; D001324:Autoantigens; D001327:Autoimmune Diseases / Q000150:complications; D060908:CTLA-4 Antigen; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D006801:Humans; D018796:Immunoconjugates; D007223:Infant; D007515:Islets of Langerhans / Q000276:immunology; D007564:Japan; D007662:Ketosis / Q000150:complications; D008565:Membrane Proteins / Q000276:immunology*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000276:immunology*; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D012016:Reference Values; D013959:Thyroid Diseases / Q000150:complications
D015703:Antigens, CD; D000943:Antigens, Differentiation; D001323:Autoantibodies; D001324:Autoantigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D008565:Membrane Proteins; D000069594:Abatacept; C516862:PTPRN protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8