Differences in the contribution of the CTLA4 gene to susceptibility to fulminant and type 1A diabetes in Japanese patients.
OBJECTIVE
To examine the contribution of the CTLA4 gene in the susceptibility to fulminant type 1 diabetes and compare it with classic type 1A diabetes.


METHODS
We genotyped the +49G>A and CT60G>A variants of the CTLA4 gene in fulminant type 1 diabetic patients (n = 55), classic type 1A diabetic patients (n = 91), and healthy control subjects (n = 369). We also assessed serum levels of the soluble form of CTLA4 (sCTLA4).


RESULTS
The +49GG and CT60GG genotypes were associated with type 1A diabetes (P < 0.001). In contrast, the CT60AA genotype, but not the +49G>A variation, was associated with fulminant type 1 diabetes (P < 0.05), especially in patients carrying HLA-DR4 (P < 0.01). Serum levels of sCTLA4 were significantly decreased in patients with fulminant type 1 diabetes (P < 0.05).


CONCLUSIONS
These results suggest that CTLA4 CT60 affects the genetic susceptibility to fulminant type 1 diabetes. Furthermore, the contribution of CTLA4 to disease susceptibility is distinct between fulminant type 1 diabetes and classic type 1A diabetes.
Kawasaki
Eiji
E
Department of Metabolism, Diabetes and Clinical Nutrition, Nagasaki University Hospital of Medicine and Dentistry, Nagasaki, Japan. eijikawa@nagasaki-u.ac.jp
Imagawa
Akihisa
A
Makino
Hideichi
H
Uga
Miho
M
Abiru
Norio
N
Hanafusa
Toshiaki
T
Uchigata
Yasuko
Y
Eguchi
Katsumi
K
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D015703:Antigens, CD / Q000235:genetics*; D060908:CTLA-4 Antigen; D003922:Diabetes Mellitus, Type 1 / Q000145:classification / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide
D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human