Advanced

Haplotype structures and large-scale association testing of the 5 ' AMP-activated protein kinase genes PRK4A2, PRKAB1, and PRK4B1 with type 2 diabetes

Sun, MW; Lee, JY; de Bakker, PIW; Burtt, NP; Almgren, Peter LU ; Råstam, Lennart LU ; Tuomi, T; Gaudet, D; Daly, MJ and Hirschhorn, JN, et al. (2006) In Diabetes 55(3). p.849-855
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes
volume
55
issue
3
pages
849 - 855
publisher
American Diabetes Association Inc.
external identifiers
  • wos:000235757600038
  • pmid:16505254
  • scopus:33644753961
ISSN
1939-327X
DOI
10.2337/diabetes.55.03.06.db05-1418
language
English
LU publication?
yes
id
eb0d3777-786e-4bdc-baa5-09baeefa3c18 (old id 416855)
date added to LUP
2007-08-17 12:43:07
date last changed
2019-10-13 04:09:17
@article{eb0d3777-786e-4bdc-baa5-09baeefa3c18,
  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.},
  author       = {Sun, MW and Lee, JY and de Bakker, PIW and Burtt, NP and Almgren, Peter and Råstam, Lennart and Tuomi, T and Gaudet, D and Daly, MJ and Hirschhorn, JN and Altshuler, D and Groop, L and Florez, JC},
  issn         = {1939-327X},
  language     = {eng},
  number       = {3},
  pages        = {849--855},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  title        = {Haplotype structures and large-scale association testing of the 5 ' AMP-activated protein kinase genes PRK4A2, PRKAB1, and PRK4B1 with type 2 diabetes},
  url          = {http://dx.doi.org/10.2337/diabetes.55.03.06.db05-1418},
  volume       = {55},
  year         = {2006},
}