Skip to main content
Article thumbnail
Location of Repository

The promoter polymorphism -232C/G of the PCK1 gene is associated with type 2 diabetes in a UK-resident South Asian population

By Simon D. Rees, Abigail C. Britten, Srikanth Bellary, J. Paul O'Hare, Sudhesh Kumar, A. H. Barnett and M. Ann Kelly

Abstract

Background\ud \ud 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.\ud Methods\ud \ud 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.\ud Results\ud \ud 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).\ud Conclusion\ud \ud 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

Topics: RC
Publisher: BioMed Central Ltd.
Year: 2009
OAI identifier: oai:wrap.warwick.ac.uk:2160

Suggested articles

Citations

  1. (2009). A Leu184Val polymorphism doi
  2. (2008). AH: Enhanced diabetes care to patients of south Asian ethnic origin (the United Kingdom Asian Diabetes Study): a cluster randomised controlled trial. Lancet doi
  3. (2006). Association of the promoter polymorphism -232C/G of the phosphoenolpyruvate carboxykinase gene (PCK1) with Type 2 diabetes mellitus. Diabet Med doi
  4. (2008). Common variants of the TCF7L2 gene are associated with increased risk of type 2 diabetes mellitus in a UK-resident South Asian population. doi
  5. Confounding from cryptic relatedness in case-control association studies. PLoS Genet 2005, 1:e32. Pre-publication history The pre-publication history for this paper can be accessed here: http://www.biomedcentral.com/1471-2350/10/83/pre pub
  6. (2004). Disregulated glyceroneogenesis: PCK1 as a candidate diabetes and obesity gene. Trends Endocrinol Metab doi
  7. (2007). et al.: Screening of 134 single nucleotide polymorphisms (SNPs) previously associated with type 2 diabetes replicates association with 12 SNPs in nine genes. Diabetes doi
  8. (1997). Froguel P: A susceptibility locus for early-onset non-insulin dependent (type 2) diabetes mellitus maps to chromosome 20q, proximal to the phosphoenolpyruvate carboxykinase gene. Hum Mol Genet doi
  9. (1996). Froguel P: Indication for genetic linkage of the phosphoenolpyruvate carboxykinase (PCK1) gene region on chromosome 20q to non-insulin-dependent diabetes mellitus. Diabetes Metab
  10. (2004). Hegele RA: Promoter polymorphism in PCK1 (phosphoenolpyruvate carboxykinase gene) associated with type 2 diabetes mellitus. doi
  11. (2005). KS: Association of a polymorphism in the gene encoding phosphoenolpyruvate carboxykinase 1 with high-density lipoprotein and triglyceride levels. Diabetologia doi
  12. (2005). MJ: Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics doi
  13. (2003). PC: Genetic Power Calculator: design of linkage and association genetic mapping studies of complex traits. Bioinformatics doi
  14. (2008). Perales JC: Pck1 gene silencing in the liver improves glycemia control, insulin sensitivity, and dyslipidemia in db/db mice. Diabetes doi
  15. (2003). The International HapMap Consortium: The International HapMap Project. Nature doi
  16. (1994). Transgenic mice overexpressing phosphoenolpyruvate carboxykinase develop noninsulin-dependent diabetes mellitus. doi
  17. (2006). Type 2 diabetes and cardiovascular risk in the UK south Asian community. Diabetologia doi

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.