title: The promoter polymorphism -232C/G of the PCK1 gene is associated with type 2 diabetes in a UK-resident South Asian population.
abstract: BACKGROUND
  The PCK1 gene, encoding cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C), has previously been implicated as a candidate gene for type 2 diabetes (T2D) susceptibility. Rodent models demonstrate that over-expression of Pck1 can result in T2D development and a single nucleotide polymorphism (SNP) in the promoter region of human PCK1 (-232C/G) has exhibited significant association with the disease in several cohorts. Within the UK-resident South Asian population, T2D is 4 to 6 times more common than in indigenous white Caucasians. Despite this, few studies have reported on the genetic susceptibility to T2D in this ethnic group and none of these has investigated the possible effect of PCK1 variants. We therefore aimed to investigate the association between common variants of the PCK1 gene and T2D in a UK-resident South Asian population of Punjabi ancestry, originating predominantly from the Mirpur area of Azad Kashmir, Pakistan.
  
  
  METHODS
  We used TaqMan assays to genotype five tagSNPs covering the PCK1 gene, including the -232C/G variant, in 903 subjects with T2D and 471 normoglycaemic controls.
  
  
  RESULTS
  Of the variants studied, only the minor allele (G) of the -232C/G SNP demonstrated a significant association with T2D, displaying an OR of 1.21 (95% CI: 1.03 - 1.42, p = 0.019).
  
  
  CONCLUSIONS
  This study is the first to investigate the association between variants of the PCK1 gene and T2D in South Asians. Our results suggest that the -232C/G promoter polymorphism confers susceptibility to T2D in this ethnic group.
  
  
  BACKGROUND
  UKADS Trial Registration: ISRCTN38297969.
authors.affiliation: College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK. s.d.rees@bham.ac.uk
authors.forename: Simon D
authors.initials: SD
authors.lastname: Rees
authors.forename: Abigail C
authors.initials: AC
authors.lastname: Britten
authors.forename: Srikanth
authors.initials: S
authors.lastname: Bellary
authors.forename: J Paul
authors.initials: JP
authors.lastname: O'Hare
authors.forename: Sudhesh
authors.initials: S
authors.lastname: Kumar
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Barnett
authors.forename: M Ann
authors.initials: MA
authors.lastname: Kelly
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010154:Pakistan / Q000208:ethnology; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D006113:United Kingdom
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C521898:PCK1 protein, human; D010729:Phosphoenolpyruvate Carboxykinase (GTP)