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

Rees, Simon D., Britten, Abigail C., Bellary, Srikanth, O'Hare, J. Paul, Kumar, Sudhesh, Barnett, Anthony H. and Kelly, M. Ann (2009). The promoter polymorphism -232C/G of the PCK1 gene is associated with type 2 diabetes in a UK-resident South Asian population. BMC Medical Genetics, 10 ,

Abstract

Background - The PCK1 gene, encoding cytosolic phosphoenolpyruvate carboxykinase (PEPCKC), 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). Conclusion - 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.

Publication DOI: https://doi.org/10.1186/1471-2350-10-83
Divisions: Life & Health Sciences > Biosciences
Life & Health Sciences > Chronic and Communicable Conditions
Life & Health Sciences
Additional Information: © 2009 Rees et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Uncontrolled Keywords: adult,aged,alleles,case-control studies,type 2 diabetes mellitus,female,genetic predisposition to disease,genotype,Great Britain,humans,intracellular signaling peptides and proteins,male,middle aged,Pakistan,phosphoenolpyruvate carboxykinase (GTP),single nucleotide polymorphism,genetic promoter regions,Genetics,Genetics(clinical)
Full Text Link: http://www.biom ... 1471-2350/10/83
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
Published Date: 2009-09-02
Authors: Rees, Simon D.
Britten, Abigail C.
Bellary, Srikanth ( 0000-0002-5924-5278)
O'Hare, J. Paul
Kumar, Sudhesh
Barnett, Anthony H.
Kelly, M. Ann

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