Lack of association between <it>PKLR </it>rs3020781 and <it>NOS1AP </it>rs7538490 and type 2 diabetes, overweight, obesity and related metabolic phenotypes in a Danish large-scale study: case-control studies and analyses of quantitative traits

• Main Authors: Almind Katrine (Author), Lauritzen Torsten (Author), Sandbæk Annelli (Author), Borch-Johnsen Knut (Author), Mogensen Mette (Author), Andreasen Camilla (Author), Hansen Lars (Author), Jørgensen Torben (Author), Pedersen Oluf (Author), Hansen Torben (Author)
• Format: Book
• Published: BMC, 2008-12-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

<p>Abstract</p> <p>Background</p> <p>Several studies in multiple ethnicities have reported linkage to type 2 diabetes on chromosome 1q21-25. Both <it>PKLR </it>encoding the liver pyruvate kinase and <it>NOS1AP </it>encoding the nitric oxide synthase 1 (neuronal) adaptor protein (CAPON) are positioned within this chromosomal region and are thus positional candidates for the observed linkage peak. The C-allele of <it>PKLR </it>rs3020781 and the T-allele of <it>NOS1AP </it>rs7538490 are reported to strongly associate with type 2 diabetes in various European-descent populations comprising a total of 2,198 individuals with a combined odds ratio (OR) of 1.33 [1.16-1.54] and 1.53 [1.28-1.81], respectively. Our aim was to validate these findings by investigating the impact of the two variants on type 2 diabetes and related quantitative metabolic phenotypes in a large study sample of Danes. Further, we intended to expand the analyses by examining the effect of the variants in relation to overweight and obesity.</p> <p>Methods</p> <p><it>PKLR </it>rs3020781 and <it>NOS1AP </it>rs7538490 were genotyped, using TaqMan allelic discrimination, in a combined study sample comprising a total of 16,801 and 16,913 individuals, respectively. The participants were ascertained from four different study groups; the population-based Inter99 cohort (<it>n</it>_{<it>PKLR </it>}= 5,962, <it>n</it>_{<it>NOS1AP </it>}= 6,008), a type 2 diabetic patient group (<it>n</it>_{<it>PKLR </it>}= 1,873, <it>n</it>_{<it>NOS1AP </it>}= 1,874) from Steno Diabetes Center, a population-based study sample (<it>n</it>_{<it>PKLR </it>}= 599, <it>n</it>_{<it>NOS1AP </it>}= 596) from Steno Diabetes Center and the ADDITION Denmark screening study cohort (<it>n</it>_{<it>PKLR </it>}= 8,367, <it>n</it>_{<it>NOS1AP </it>}= 8,435).</p> <p>Results</p> <p>In case-control studies we evaluated the potential association between rs3020781 and rs7538490 and type 2 diabetes and obesity. No significant associations were observed for type 2 diabetes (rs3020781: <it>p</it>_AF= 0.49, OR = 1.02 [0.96-1.10]; rs7538490: <it>p</it>_AF= 0.84, OR = 0.99 [0.93-1.06]). Neither did we show association with overweight or obesity. Additionally, the <it>PKLR </it>and the <it>NOS1AP </it>genotypes were demonstrated not to have a major influence on diabetes-related quantitative metabolic phenotypes.</p> <p>Conclusion</p> <p>We failed to provide evidence of an association between <it>PKLR </it>rs3020781 and <it>NOS1AP </it>rs7538490 and type 2 diabetes, overweight, obesity or related quantitative metabolic phenotypes in large-scale studies of Danes.</p>

Item Description

10.1186/1471-2350-9-118
1471-2350