title: The association of Ala45Thr polymorphism in NeuroD with child-onset Type 1a diabetes in Japanese.
abstract: Recently Iwata et al. reported that the polymorphism in NeuroD exon 2(Ala45Thr) was associated with adult-onset Type 1 diabetes in Japanese. Furthermore, the mutations in the NeuroD as a regulator of insulin transcription have been reported to result in Type 2 diabetes. We, therefore, aimed to clarify the role of this Ala45Thr polymorphism in the susceptibility to Type 1a, immune-mediated, diabetes of child-onset Japanese patients. Eighty patients with child-onset Type 1 diabetes were examined along with 121 non-diabetic subjects as the controls. The polymorphism in Ala45Thr was defined using the PCR-RFLP method. The GAD Ab, IA-2 Ab, HLA-DRB1 genotypes and residual beta-cell function at 3 years from onset were evaluated in relation to the difference in this polymorphism. The frequency of the Ala45Thr heterozygotes was significantly higher in the Type 1 diabetic patients than in the controls (21.3 versus 9.9%, P=0.0252). The frequency of loss of beta-cell function was higher in heterozygotes patients than in wild type homozygotes patients (P=0.0112). Type 1 diabetic patients with DRB1*0901 allele showed a significantly higher frequency, 27.9%, of the Ala45Thr variant than the controls (P=0.0041). In conclusion, the Ala45Thr polymorphism contributes to the risk of development of, and to the early deterioration of beta-cell function, in Type 1a diabetes among the Japanese population.
authors.affiliation: Departments of Pediatrics, Yamanashi Medical University, Shimokato 1110, Tamaho-machi, Nakakoma-gun, 409-3898, Yamanashi, Japan.
authors.forename: Mie
authors.initials: M
authors.lastname: Mochizuki
authors.forename: Shin
authors.initials: S
authors.lastname: Amemiya
authors.forename: Kisho
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Koji
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Toshihide
authors.initials: T
authors.lastname: Ishihara
authors.forename: Misaki
authors.initials: M
authors.lastname: Aya
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Kato
authors.forename: Akira
authors.initials: A
authors.lastname: Kasuga
authors.forename: Shinpei
authors.initials: S
authors.lastname: Nakazawa
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D000409:Alanine; D000483:Alleles; D044466:Asian People; D051792:Basic Helix-Loop-Helix Proteins; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D018257:Helix-Loop-Helix Motifs; D006720:Homozygote; D006801:Humans; D007564:Japan; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012016:Reference Values; D013912:Threonine; D013997:Time Factors
chemical_list: D000409:Alanine; D051792:Basic Helix-Loop-Helix Proteins; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D009419:Nerve Tissue Proteins; D013912:Threonine; C093564:Neurogenic differentiation factor 1