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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)
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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
2016-04-01 16:00:42
date last changed
2024-01-10 23:47:09
@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}},
  doi          = {{10.2337/diabetes.55.03.06.db05-1418}},
  volume       = {{55}},
  year         = {{2006}},
}