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

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.

Lee, JY (författare)
de Bakker, PIW (författare)
Burtt, NP (författare)
Almgren, PeterLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)endo-pal (författare)
Råstam, LennartLund University,Lunds universitet,Samhällsmedicin,Forskargrupper vid Lunds universitet,Community Medicine,Lund University Research Groups(Swepub:lu)smi-lra (författare)
Tuomi, T (författare)
Gaudet, D (författare)
Daly, MJ (författare)
Hirschhorn, JN (författare)
Altshuler, D (författare)
Groop, L (författare)
Florez, JC (författare)
Genomik, diabetes och endokrinologiForskargrupper vid Lunds universitet (creator_code:org_t)

Ingår i:Diabetes: American Diabetes Association55:3, s. 849-8551939-327X0012-1797

Av författaren/redakt...: Sun, MW; Lee, JY; de Bakker, PIW; Burtt, NP; Almgren, Peter; Råstam, Lennart; visa fler...; Tuomi, T; Gaudet, D; Daly, MJ; Hirschhorn, JN; Altshuler, D; Groop, L; Florez, JC; visa färre...

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