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. 2008 Dec 26:9:118.
doi: 10.1186/1471-2350-9-118.

Lack of association between PKLR rs3020781 and NOS1AP 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

Camilla Helene Andreasen  1 , Mette Sloth Mogensen, Knut Borch-Johnsen, Annelli Sandbaek, Torsten Lauritzen, Katrine Almind, Lars Hansen, Torben Jørgensen, Oluf Pedersen, Torben Hansen
Affiliations

Lack of association between PKLR rs3020781 and NOS1AP 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

Camilla Helene Andreasen et al. BMC Med Genet. .

Abstract

Background: Several studies in multiple ethnicities have reported linkage to type 2 diabetes on chromosome 1q21-25. Both PKLR encoding the liver pyruvate kinase and NOS1AP 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 PKLR rs3020781 and the T-allele of NOS1AP 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.

Methods: PKLR rs3020781 and NOS1AP 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 (nPKLR = 5,962, nNOS1AP = 6,008), a type 2 diabetic patient group (nPKLR = 1,873, nNOS1AP = 1,874) from Steno Diabetes Center, a population-based study sample (nPKLR = 599, nNOS1AP = 596) from Steno Diabetes Center and the ADDITION Denmark screening study cohort (nPKLR = 8,367, nNOS1AP = 8,435).

Results: 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: pAF = 0.49, OR = 1.02 [0.96-1.10]; rs7538490: pAF = 0.84, OR = 0.99 [0.93-1.06]). Neither did we show association with overweight or obesity. Additionally, the PKLR and the NOS1AP genotypes were demonstrated not to have a major influence on diabetes-related quantitative metabolic phenotypes.

Conclusion: We failed to provide evidence of an association between PKLR rs3020781 and NOS1AP rs7538490 and type 2 diabetes, overweight, obesity or related quantitative metabolic phenotypes in large-scale studies of Danes.

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References

    1. Das SK, Elbein SC. The search for type 2 diabetes susceptibility loci: the chromosome 1q story. Curr Diab Rep. 2007;7:154–164. doi: 10.1007/s11892-007-0025-3. - DOI - PubMed
    1. Das SK, Hasstedt SJ, Zhang Z, Elbein SC. Linkage and association mapping of a chromosome 1q21-q24 type 2 diabetes susceptibility locus in northern European Caucasians. Diabetes. 2004;53:492–499. doi: 10.2337/diabetes.53.2.492. - DOI - PubMed
    1. Elbein SC, Hoffman MD, Teng K, Leppert MF, Hasstedt SJ. A genome-wide search for type 2 diabetes susceptibility genes in Utah Caucasians. Diabetes. 1999;48:1175–1182. doi: 10.2337/diabetes.48.5.1175. - DOI - PubMed
    1. Hanson RL, Ehm MG, Pettitt DJ, Prochazka M, Thompson DB, Timberlake D, et al. An autosomal genomic scan for loci linked to type II diabetes mellitus and body-mass index in Pima Indians. Am J Hum Genet. 1998;63:1130–1138. doi: 10.1086/302061. - DOI - PMC - PubMed
    1. Hanson RL, Imperatore G, Narayan KM, Roumain J, Fagot-Campagna A, Pettitt DJ, et al. Family and genetic studies of indices of insulin sensitivity and insulin secretion in Pima Indians. Diabetes Metab Res Rev. 2001;17:296–303. doi: 10.1002/dmrr.213. - DOI - PubMed

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