Details

Autor(en) / Beteiligte

• Vella, Adrian
• Howson, Joanna M.M.
• Barratt, Bryan J.
• Twells, Rebecca C.J.
• Rance, Helen E.
• Nutland, Sarah
• Tuomilehto-Wolf, Eva
• Tuomilehto, Jaakko
• Undlien, Dag E.
• Rønningen, Kjersti S.
• Guja, Cristian
• Ionescu-Tîrgovişte, Constantin
• Savage, David A.
• Todd, John A.

Titel

Lack of Association of the Ala45Thr Polymorphism and Other Common Variants of the NeuroD Gene With Type 1 Diabetes

Ist Teil von

• Diabetes (New York, N.Y.), 2004-04, Vol.53 (4), p.1158-1161

Ort / Verlag

Alexandria, VA: American Diabetes Association

Erscheinungsjahr

2004

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Lack of Association of the Ala 45 Thr Polymorphism and Other Common Variants of the NeuroD Gene With Type 1 Diabetes Adrian Vella 1 , Joanna M.M. Howson 1 , Bryan J. Barratt 1 , Rebecca C.J. Twells 1 , Helen E. Rance 1 , Sarah Nutland 1 , Eva Tuomilehto-Wolf 2 , Jaakko Tuomilehto 2 3 , Dag E. Undlien 4 , Kjersti S. Rønningen 5 , Cristian Guja 6 , Constantin Ionescu-Tîrgovişte 6 , David A. Savage 7 and John A. Todd 1 1 Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, U.K 2 Diabetes and Genetic Epidemiology Unit, National Public Health Institute, University of Helsinki, Helsinki, Finland 3 Department of Public Health, University of Helsinki, Helsinki, Finland 4 Institute of Medical Genetics, Ulleval University Hospital, University of Oslo, Oslo, Norway 5 Laboratory of Molecular Epidemiology, Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway 6 Clinic of Diabetes, Institute of Diabetes, Nutrition and Metabolic Diseases ‘N. Paulescu,’ Bucharest, Romania 7 Department of Medical Genetics, Queen’s University Belfast, Belfast City Hospital, Belfast, Northern Ireland Address correspondence and reprint requests to Professor John A. Todd, JDRF/WT Diabetes and Inflammation Laboratory, University of Cambridge, Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 2XY, U.K. E-mail: john.todd{at}cimr.cam.ac.uk Abstract 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 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. MODY, maturity-onset diabetes of the young SNP, single nucleotide polymorphism TDT, transmission disequilibrium test Footnotes Additional information for this article can be found in an online appendix at http://diabetes.diabetesjournals.org . Accepted January 5, 2004. Received December 18, 2003. DIABETES