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

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Rees, Simon D., Britten, Abigail C., Bellary, Srikanth, O'Hare, J. Paul, Kumar, Sudhesh, Barnett, A. H. (Anthony H.), 1951- 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, Vol.10 . p. 83. ISSN 1471-2350

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Official URL: http://dx.doi.org/10.1186/1471-2350-10-83

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).
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.

Item Type:	Journal Article
Subjects:	R Medicine > RC Internal medicine
Divisions:	Faculty of Medicine > Warwick Medical School > Translational & Systems Medicine > Metabolic and Vascular Health Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Non-insulin-dependent diabetes -- Great Britain, Diabetes -- Genetic aspects -- Research, South Asians -- Health and hygiene -- Great Britain, Chromosome polymorphism
Journal or Publication Title:	BMC Medical Genetics
Publisher:	BioMed Central Ltd.
ISSN:	1471-2350
Official Date:	2 September 2009
Volume:	Vol.10
Page Range:	p. 83
Identification Number:	10.1186/1471-2350-10-83
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access
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URI:	http://wrap.warwick.ac.uk/id/eprint/2160