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- Title
High-Density Haplotype Structure and Association Testing of the Insulin-Degrading Enzyme (IDE) Gene With Type 2 Diabetes in 4,206 People.
- Authors
Florez, Jose C.; Wiltshire, Steven; Agapakis, Christina M.; Burtt, Noël P.; de Bakker, Paul I. W.; Almgren, Peter; Boström, Kristina Bengtsson; Tuomi, Tiinamaija; Gaudet, Daniel; Daly, Mark J.; Hirschhorn, Joel N.; McCarthy, Mark I.; Altshuler, David; Groop, Leif
- Abstract
The insulin-degrading enzyme is responsible for the intracellular proteolysis of insulin. Its gene IDE is located on chromosome 10, in an area with suggestive linkage to type 2 diabetes and related phenotypes. Due to the impact of genetic variants of this gene in rodents and the function of its protein product, it has been proposed as a candidate gene for type 2 diabetes. Various groups have explored the role of the common genetic variation of IDE on insulin resistance and reported associations of various single nucleotide polymorphisms (SNPs) and haplotypes on both type 2 diabetes and glycemic traits. We sought to characterize the haplotype structure of IDE in detail and replicate the association of common variants with type 2 diabetes, fasting insulin, fasting glucose, and insulin resistance. We assessed linkage disequilibrium, selected single-marker and multimarker tags, and genotyped these markers in several case-control and family-based samples totalling 4,206 Caucasian individuals. We observed no statistically significant evidence of association between single-marker or multimarker tests in IDE and type 2 diabetes. Nominally significant differences in quantitative traits are consistent with statistical noise. We conclude that common genetic variation at IDE is unlikely to confer clinically significant risk of type 2 diabetes in Caucasians.
- Subjects
ENZYMES; PROTEOLYSIS; CHROMOSOMES; PHENOTYPES; INSULIN resistance
- Publication
Diabetes, 2006, Vol 55, Issue 1, p128
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/diabetes.55.01.06.db05-0954