title: Association of polymorphism in the NeuroD/BETA2 gene with type 1 diabetes in the Japanese.
abstract: 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.
authors.affiliation: First Department of Internal Medicine, Kyushu University, Fukuoka, Japan. nagafuti@intmed1.med.kyushu-u.ac.jp
authors.forename: I
authors.initials: I
authors.lastname: Iwata
authors.forename: S
authors.initials: S
authors.lastname: Nagafuchi
authors.forename: H
authors.initials: H
authors.lastname: Nakashima
authors.forename: S
authors.initials: S
authors.lastname: Kondo
authors.forename: T
authors.initials: T
authors.lastname: Koga
authors.forename: Y
authors.initials: Y
authors.lastname: Yokogawa
authors.forename: T
authors.initials: T
authors.lastname: Akashi
authors.forename: T
authors.initials: T
authors.lastname: Shibuya
authors.forename: Y
authors.initials: Y
authors.lastname: Umeno
authors.forename: T
authors.initials: T
authors.lastname: Okeda
authors.forename: S
authors.initials: S
authors.lastname: Shibata
authors.forename: S
authors.initials: S
authors.lastname: Kono
authors.forename: M
authors.initials: M
authors.lastname: Yasunami
authors.forename: H
authors.initials: H
authors.lastname: Ohkubo
authors.forename: Y
authors.initials: Y
authors.lastname: Niho
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence / Q000235:genetics; D044466:Asian People / Q000235:genetics; D051792:Basic Helix-Loop-Helix Proteins; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004247:DNA; D004268:DNA-Binding Proteins; D015534:Trans-Activators; C093970:NEUROD1 protein, human