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Diabetes Care Publish Ahead of Print published online ahead of print April 28, 2008
DOI: 10.2337/dc08-0280
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Original Research

Differences in the Contribution of CTLA4 Gene to Susceptibility to Fulminant and Type 1A Diabetes in Japanese Patients

Eiji Kawasaki, MD1, Akihisa Imagawa, MD2, Hideichi Makino, MD3, Miho Uga1, Norio Abiru, MD4, Toshiaki Hanafusa, MD2, Yasuko Uchigata, MD5 and Katsumi Eguchi, MD4

1Department of Metabolism/Diabetes and Clinical Nutrition, Nagasaki University Hospital of Medicine and Dentistry
2First Department of Internal Medicine, Osaka Medical College
3Department of Laboratory Medicine, Ehime University School of Medicine
4Department of Endocrinology and Metabolism, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences
5Diabetes Center, Tokyo Women's Medical University School of Medicine

eijikawa{at}nagasaki-u.ac.jp

ABSTRACT

Objective: We examined the contribution of the CTLA4 gene in the susceptibility to fulminant type 1 diabetes (T1D), and compared them with "classic" type 1A diabetes (T1AD).

Research design and methods: We genotyped the +49G>A and CT60 G>A of the CTLA4 in fulminant T1D (n=55), "classic" T1AD (n=91), and healthy control subjects (n=369). We also assessed serum levels of soluble form of CTLA4.

Results: The +49GG and CT60GG genotypes were associated with T1AD (P<0.001). In contrast, the CT60AA genotype, but not +49G>A, was associated with fulminant T1D (P<0.05), especially in patients carrying HLA-DR4 (P<0.001). Serum levels of sCTLA4 were significantly decreased in patients with fulminant T1D (P<0.05).

Conclusions: These results suggest that CTLA4 CT60 affects the genetic susceptibility to fulminant T1D. Furthermore, the contribution of the CTLA4 to the disease susceptibility is distinct between fulminant T1D and "classic" T1AD.


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