Lack of association of the Ala(45)Thr polymorphism and other common variants of the NeuroD gene with type 1 diabetes.
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.
Vella
Adrian
A
Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
Howson
Joanna M M
JM
Barratt
Bryan J
BJ
Twells
Rebecca C J
RC
Rance
Helen E
HE
Nutland
Sarah
S
Tuomilehto-Wolf
Eva
E
Tuomilehto
Jaakko
J
Undlien
Dag E
DE
Rønningen
Kjersti S
KS
Guja
Cristian
C
Ionescu-Tîrgovişte
Constantin
C
Savage
David A
DA
Todd
John A
JA
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
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