Differences in the Contribution of CTLA4 Gene to Susceptibility to Fulminant and Type 1A Diabetes in Japanese Patients
- Eiji Kawasaki, MD (eijikawa{at}nagasaki-u.ac.jp)1,
- 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
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.
Footnotes
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- Received February 7, 2008.
- Accepted April 20, 2008.
- Copyright © American Diabetes Association
