TY - JOUR
T1 - Lack of Association of the Ala 45Thr Polymorphism and Other Common Variants of the NeuroD Gene with Type 1 Diabetes
AU - Vella, Adrian
AU - Howson, Joanna M.M.
AU - Barratt, Bryan J.
AU - Twells, Rebecca C.J.
AU - Rance, Helen E.
AU - Nutland, Sarah
AU - Tuomilehto-Wolf, Eva
AU - Tuomilehto, Jaakko
AU - Undlien, Dag E.
AU - Rønningen, Kjersti S.
AU - Guja, Cristian
AU - Ionescu-Tîrgovişte, Constantin
AU - Savage, David A.
AU - Todd, John A.
PY - 2004/4
Y1 - 2004/4
N2 - Variation in genes necessary for normal functioning and development of β-cells, e.g., NEUROD1, which encodes a transcription factor for the insulin gene and is important in β-cell development, causes maturity-onset diabetes of the young. Some studies have reported an association between a nonsynonymous Ala45Thr (+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 Ala45Thr in 2,434 type 1 diabetic families of European descent and Caucasian ethnicity from five different countries. Taking the allele frequency of 36% for Thr45 and an odds ratio (OR) of 1.2, this sample provided >99% power to detect an association (P < 0.95). 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.
AB - Variation in genes necessary for normal functioning and development of β-cells, e.g., NEUROD1, which encodes a transcription factor for the insulin gene and is important in β-cell development, causes maturity-onset diabetes of the young. Some studies have reported an association between a nonsynonymous Ala45Thr (+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 Ala45Thr in 2,434 type 1 diabetic families of European descent and Caucasian ethnicity from five different countries. Taking the allele frequency of 36% for Thr45 and an odds ratio (OR) of 1.2, this sample provided >99% power to detect an association (P < 0.95). 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.
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U2 - 10.2337/diabetes.53.4.1158
DO - 10.2337/diabetes.53.4.1158
M3 - Article
C2 - 15047635
AN - SCOPUS:12144290500
SN - 0012-1797
VL - 53
SP - 1158
EP - 1161
JO - Diabetes
JF - Diabetes
IS - 4
ER -