Diabetes, Vol 48, Issue 2 416-419, Copyright © 1999 by American Diabetes Association

ARTICLES

Association of polymorphism in the NeuroD/BETA2 gene with type 1 diabetes in the Japanese

I Iwata, S Nagafuchi, H Nakashima, S Kondo, T Koga, Y Yokogawa, T Akashi, T Shibuya, Y Umeno, T Okeda, S Shibata, S Kono, M Yasunami, H Ohkubo and Y Niho
First Department of Internal Medicine, Kyushu University, Fukuoka, Japan. nagafuti@intmed1.med.kyushu-u.ac.jp

NeuroD/BETA2, a transcription factor of the insulin gene, also plays an important role in the development of pancreatic beta-cells. Recently, the NeuroD/BETA2 gene has been mapped to the long arm of human chromosome 2 (2q32) where the IDDM7 gene has previously been mapped, implying its involvement in diabetes. To identify mutations in the NeuroD/BETA2 gene that may predispose patients to develop diabetes, we studied the gene in 50 Japanese subjects with diabetes (4 with type 1 and 46 with type 2) by the polymerase chain reaction (PCR) followed by single-strand conformation polymorphism and sequencing analyses. Further analysis was performed in 392 Japanese subjects (60 with type 1 and 158 with type 2 diabetes and 174 healthy control subjects) by mismatch PCR restriction fragment length polymorphism. We found a DNA polymorphism of the NeuroD/BETA2 gene. A nucleotide G-to-A transition results in the substitution of alanine to threonine at codon 45 (Ala45Thr). The frequencies of heterozygotes for the Ala45Thr variant were 9.8% in the control subjects, 9.5% in the patients with type 2 diabetes, and 25.0% in the patients with type 1 diabetes, a significant difference (P = 0.006). Because the variant of the NeuroD/BETA2 gene (Ala45Thr) is associated with type 1 but not type 2 diabetes, it may be implicated in the loss of pancreatic beta-cells in type 1 diabetes.
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