Details

Autor(en) / Beteiligte

• Iwata, I
• Nagafuchi, S
• Nakashima, H
• Kondo, S
• Koga, T
• Yokogawa, Y
• Akashi, T
• Shibuya, T
• Umeno, Y
• Okeda, T
• Shibata, S
• Kono, S
• Yasunami, M
• Ohkubo, H
• Niho, Y

Titel

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

Ist Teil von

• Diabetes (New York, N.Y.), 1999-02, Vol.48 (2), p.416-419

Ort / Verlag

United States

Erscheinungsjahr

1999

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.