NeuroD/BETA2 gene variability and diabetes: no associations to late-onset type 2 diabetes but an A45 allele may represent a susceptibility marker for type 1 diabetes among Danes. Danish Study Group of Diabetes in Childhood, and the Danish IDDM Epidemiology and Genetics Group
| Autor: | T. Hansen, S Urioste, Hans Eiberg, J Nerup, Flemming Pociot, Lars Hansen, Palle Serup, O. P. Kristiansen, Jan N. Jensen, Helle V. Petersen, Oluf Pedersen |
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| Rok vydání: | 2000 |
| Předmět: |
Genetic Markers
Linkage disequilibrium Denmark Endocrinology Diabetes and Metabolism Molecular Sequence Data Type 2 diabetes Biology Diabetes mellitus genetics Diabetes mellitus Basic Helix-Loop-Helix Transcription Factors Diabetes Mellitus Internal Medicine medicine Humans Genetic Predisposition to Disease Age of Onset Allele frequency Alleles NeuroD Genetics Type 1 diabetes Genetic Variation Transmission disequilibrium test medicine.disease DNA-Binding Proteins Diabetes Mellitus Type 1 Diabetes Mellitus Type 2 Trans-Activators |
| Zdroj: | Diabetes. 49:876-878 |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/diabetes.49.5.876 |
| Popis: | Mutations in the NeuroD/BETA2 gene have been shown to associate with type 2 diabetes. In the present study, we examined mutations in the NeuroD/BETA2 gene for association with either type 1 or 2 diabetes. Three variants were identified in patients with type 2 diabetes: Ala45Thr (allelic frequency 0.36, 95% CI 0.31-0.41), Pro197His (0.01), and Ser259Ser (0.01). Ala45Thr and Pro197His were not associated with type 2 diabetes, but the transmission disequilibrium test showed unequal transmission of the A45 allele to offspring with type 1 diabetes (chi2 = 5.90, P < 0.02, odds ratio 1.55, 95% CI 0.91-2.63). This association could not be explained by linkage disequilibrium between the Ala45 allele and IDDM7 (D2S152), which is also located on chromosome 2q32. When tested in vitro, the biological activity of Thr45 (117+/-36% vs. Ala45) and His197 (90+/-28% vs. Pro197) on the regulation of the human insulin gene promoter appeared normal. In conclusion, mutations in the NeuroD/BETA2 gene are not a common cause of late-onset type 2 diabetes among Danes. However, in the type 1 diabetic Danish population, the Ala45Thr variant of NeuroD/BETA2 may represent a susceptibility marker independent of IDDM7 on chromosome 2q32. |
| Databáze: | OpenAIRE |
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