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- Title
Haplotype Structures and Large-Scale Association Testing of the 5' AMP-Activated Protein Kinase Genes PRKAA2, PRKAB1, and PRKAB1 With Type 2 Diabetes.
- Authors
Sun, Maria W.; Lee, Jennifer Y.; de Bakker, Paul I. W.; Burtt, Noël P.; Almgren, Peter; Råstam, Lennart; Tuomi, Tiinamaija; Gaudet, Daniel; Daly, Mark J.; Hirschhorn, Joel N.; Altshuler, David; Groop, Leif; Florez, Jose C.
- Abstract
AMP-activated protein kinase (AMPK) is a key molecular regulator of cellular metabolism, and its activity is induced by both metformin and thiazolidinedione antidiabetic medications. It has therefore been proposed both as a putative agent in the pathophysiology of type 2 diabetes and as a valid target for therapeutic intervention. Thus, the genes that encode the various AMPK subunits are intriguing candidates for the inherited basis of type 2 diabetes. We therefore set out to test for the association of common variants in the genes that encode three selected AMPK subunits with type 2 diabetes and related phenotypes. Of the seven genes that encode AMPK isoforms, we initially chose PRKAA2, PRKAB1, and PRKAB2 because of their higher prior probability of association with type 2 diabetes, based on previous reports of genetic linkage, functional molecular studies, expression patterns, and pharmacological evidence. We determined their haplotype structure, selected a subset of tag single nucleotide polymorphisms that comprehensively capture the extent of common genetic variation in these genes, and genotyped them in family-based and case/control samples comprising 4,206 individuals. Analysis of single-marker and multi-marker tests revealed no association with type 2 diabetes, fasting plasma glucose, or insulin sensitivity. Several nominal associations of variants in PRKAA2 and PRKAB1 with BMI appear to be consistent with statistical noise.
- Subjects
PROTEIN kinases; CELL metabolism; CELLULAR control mechanisms; DIABETES; MEDICAL research
- Publication
Diabetes, 2006, Vol 55, Issue 3, p849
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/diabetes.55.03.06.db05-1418