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

Research output: Contribution to journalArticle

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.

Details

Authors
  • MW Sun
  • JY Lee
  • PIW de Bakker
  • NP Burtt
  • Peter Almgren
  • Lennart Råstam
  • T Tuomi
  • D Gaudet
  • MJ Daly
  • JN Hirschhorn
  • D Altshuler
  • L Groop
  • JC Florez
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes
Original languageEnglish
Pages (from-to)849-855
JournalDiabetes
Volume55
Issue number3
Publication statusPublished - 2006
Publication categoryResearch
Peer-reviewedYes