The minor C-allele of rs2014355 in ACADSis associated with reduced insulin release following an oral glucose load

BMC Medical Genetics

Research Article

Annelli Sandbæk¹  Torsten Lauritzen¹  Åsa Andersson²  Nikolaj T Krarup³  Thorkild IA Sørensen⁴  Johanne M Justesen⁵  Karina Banasik⁵  Malene Hornbak⁶  Torben Hansen⁷  Oluf Pedersen⁸  Camilla H Sandholt⁹  Charlotta Pisinger^1,10  Daniel R Witte^1,11 

[1] Department of General Practice, University of Aarhus, Aarhus, Denmark;Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark;Hagedorn Research Institute, Gentofte, Denmark;Institute of Biomedical Science, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark;Institute of Preventive Medicine, Copenhagen University Hospital, Center for Health and Society, Copenhagen, Denmark;Marie Krogh Center for Metabolic Research, Section of Metabolic Genetics, Faculty of Health Sciences, University of Copenhagen, Denmark;Marie Krogh Center for Metabolic Research, Section of Metabolic Genetics, Faculty of Health Sciences, University of Copenhagen, Denmark;Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark;Marie Krogh Center for Metabolic Research, Section of Metabolic Genetics, Faculty of Health Sciences, University of Copenhagen, Denmark;Hagedorn Research Institute, Gentofte, Denmark;Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark;Marie Krogh Center for Metabolic Research, Section of Metabolic Genetics, Faculty of Health Sciences, University of Copenhagen, Denmark;Hagedorn Research Institute, Gentofte, Denmark;Institute of Biomedical Science, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark;Faculty of Health Sciences, University of Aarhus, Aarhus, Denmark;Marie Krogh Center for Metabolic Research, Section of Metabolic Genetics, Faculty of Health Sciences, University of Copenhagen, Denmark;Novo Nordisk A/S, Medical and Science, Development Projects, Bagsværd, Denmark;Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark;Institute of Preventive Medicine, Copenhagen University Hospital, Center for Health and Society, Copenhagen, Denmark;Steno Diabetes Center, Gentofte, Denmark;

关键词: Oral Glucose Tolerance Test;    Insulin Release;    Serum Insulin;    Short Chain Fatty Acid;    Oral Glucose Load;   

DOI  :  10.1186/1471-2350-12-4

 received in 2010-06-02, accepted in 2011-01-06,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundA genome-wide association study (GWAS) using metabolite concentrations as proxies for enzymatic activity, suggested that two variants: rs2014355 in the gene encoding short-chain acyl-coenzyme A dehydrogenase (ACADS) and rs11161510 in the gene encoding medium-chain acyl-coenzyme A dehydrogenase (ACADM) impair fatty acid β-oxidation. Chronic exposure to fatty acids due to an impaired β-oxidation may down-regulate the glucose-stimulated insulin release and result in an increased risk of type 2 diabetes (T2D). We aimed to investigate whether the two variants associate with altered insulin release following an oral glucose load or with T2D.MethodsThe variants were genotyped using KASPar® PCR SNP genotyping system and investigated for associations with estimates of insulin release and insulin sensitivity following an oral glucose tolerance test (OGTT) in a random sample of middle-aged Danish individuals (nACADS= 4,324; nACADM= 4,337). The T2D-case-control study involved a total of ~8,300 Danish individuals (nACADS= 8,313; nACADM= 8,344).ResultsIn glucose-tolerant individuals the minor C-allele of rs2014355 of ACADS associated with reduced measures of serum insulin at 30 min following an oral glucose load (per allele effect (β) = -3.8% (-6.3%;-1.3%), P = 0.003), reduced incremental area under the insulin curve (β = -3.6% (-6.3%;-0.9%), P = 0.009), reduced acute insulin response (β = -2.2% (-4.2%;0.2%), P = 0.03), and with increased insulin sensitivity ISIMatsuda (β = 2.9% (0.5%;5.2%), P = 0.02). The C-allele did not associate with two other measures of insulin sensitivity or with a derived disposition index. The C-allele was not associated with T2D in the case-control analysis (OR 1.07, 95% CI 0.96-1.18, P = 0.21). rs11161510 of ACADM did not associate with any indices of glucose-stimulated insulin release or with T2D.ConclusionsIn glucose-tolerant individuals the minor C-allele of rs2014355 of ACADS was associated with reduced measures of glucose-stimulated insulin release during an OGTT, a finding which in part may be mediated through an impaired β-oxidation of fatty acids.

【 授权许可】

Unknown   
© Hornbak et al; licensee BioMed Central Ltd. 2011. This article is published under license to 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.