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

doi:10.2337/dc08-0280

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

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

Corresponding author: Eiji Kawasaki, eijikawa{at}nagasaki-u.ac.jp

Abstract

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.

RESEARCH DESIGN AND 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.

Footnotes

Published ahead of print at http://care.diabetesjournals.org on 28 April 2008.

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- Received February 7, 2008.
- Accepted April 20, 2008.