Haplotype structures and large-scale association testing of the 5 ' AMP-activated protein kinase genes PRK4A2, PRKAB1, and PRK4B1 with type 2 diabetes
(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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https://lup.lub.lu.se/record/416855
- author
- organization
- publishing date
- 2006
- 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}}, }