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

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• 作者：Malene Hornbak (1) (2)
  Karina Banasik (1)
  Johanne M Justesen (1)
  Nikolaj T Krarup (3)
  Camilla H Sandholt (1) (5)
  ?sa Andersson (2)
  Annelli Sandb?k (6)
  Torsten Lauritzen (6)
  Charlotta Pisinger (7) (9)
  Daniel R Witte (8)
  Thorkild IA S?rensen (4) (9)
  Oluf Pedersen (1) (10) (3) (4)
  Torben Hansen (1) (11) (3)
  
• 刊名：BMC Medical Genetics
• 出版年：2011
• 出版时间：December 2011
• 年：2011
• 卷：12
• 期：1
• 全文大小：177KB
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  29. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2350/12/4/prepub
  
• 作者单位：Malene Hornbak (1) (2)
  Karina Banasik (1)
  Johanne M Justesen (1)
  Nikolaj T Krarup (3)
  Camilla H Sandholt (1) (5)
  ?sa Andersson (2)
  Annelli Sandb?k (6)
  Torsten Lauritzen (6)
  Charlotta Pisinger (7) (9)
  Daniel R Witte (8)
  Thorkild IA S?rensen (4) (9)
  Oluf Pedersen (1) (10) (3) (4)
  Torben Hansen (1) (11) (3)
  
  1. Marie Krogh Center for Metabolic Research, Section of Metabolic Genetics, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
  2. Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark
  3. Hagedorn Research Institute, Gentofte, Denmark
  5. Novo Nordisk A/S, Medical and Science, Development Projects, Bagsv?rd, Denmark
  6. Department of General Practice, University of Aarhus, Aarhus, Denmark
  7. Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark
  9. Medicine Center for Health and Society, Institute of Preventive, Copenhagen University Hospital, Copenhagen, Denmark
  8. Steno Diabetes Center, Gentofte, Denmark
  4. Faculty of Health Sciences, Institute of Biomedical Science, University of Copenhagen, Copenhagen, Denmark
  10. Faculty of Health Sciences, University of Aarhus, Aarhus, Denmark
  11. Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
  
• ISSN：1471-2350

文摘

Background A 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. Methods The 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 (n ACADS = 4,324; n ACADM = 4,337). The T2D-case-control study involved a total of ~8,300 Danish individuals (n ACADS = 8,313; n ACADM = 8,344). Results In 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. Conclusions In 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.