title: Lack of association of the Ala(45)Thr polymorphism and other common variants of the NeuroD gene with type 1 diabetes.
abstract: Variation in genes necessary for normal functioning and development of beta-cells, e.g., NEUROD1, which encodes a transcription factor for the insulin gene and is important in beta-cell development, causes maturity-onset diabetes of the young. Some studies have reported an association between a nonsynonymous Ala(45)Thr (+182G-->A) single nucleotide polymorphism (SNP) in NEUROD1 and type 1 diabetes, but this result has not been consistently found. To clarify this, we genotyped Ala(45)Thr in 2,434 type 1 diabetic families of European descent and Caucasian ethnicity from five different countries. Taking the allele frequency of 36% for Thr(45) and an odds ratio (OR) of 1.2, this sample provided >99% power to detect an association (P < 0.05). We could not confirm the association (P = 0.77). No evidence of population heterogeneity in the lack of association of Thr(45) with type 1 diabetes was observed. To evaluate the possibility that another NEUROD1 variant was associated with type 1 diabetes, we resequenced the gene in 32 U.K. affected individuals and identified and genotyped all common SNPs (minor allele frequency >10%; n = 5) in 786 families. We report no evidence of association of these common variants in NEUROD1 and type 1 diabetes in these samples.
authors.affiliation: Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
authors.forename: Adrian
authors.initials: A
authors.lastname: Vella
authors.forename: Joanna M M
authors.initials: JM
authors.lastname: Howson
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Barratt
authors.forename: Rebecca C J
authors.initials: RC
authors.lastname: Twells
authors.forename: Helen E
authors.initials: HE
authors.lastname: Rance
authors.forename: Sarah
authors.initials: S
authors.lastname: Nutland
authors.forename: Eva
authors.initials: E
authors.lastname: Tuomilehto-Wolf
authors.forename: Jaakko
authors.initials: J
authors.lastname: Tuomilehto
authors.forename: Dag E
authors.initials: DE
authors.lastname: Undlien
authors.forename: Kjersti S
authors.initials: KS
authors.lastname: Rønningen
authors.forename: Cristian
authors.initials: C
authors.lastname: Guja
authors.forename: Constantin
authors.initials: C
authors.lastname: Ionescu-Tîrgovişte
authors.forename: David A
authors.initials: DA
authors.lastname: Savage
authors.forename: John A
authors.initials: JA
authors.lastname: Todd
mesh_terms: D019943:Amino Acid Substitution; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D017931:DNA Primers; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D017931:DNA Primers; D018398:Homeodomain Proteins; D018975:Insulin-Like Growth Factor Binding Protein 5; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; C075279:HOXD8 protein, human; C093564:Neurogenic differentiation factor 1