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

Malene Hornbak; Karina Banasik; Johanne Marie Justesen; Nikolaj Thure Krarup; Camilla Helene Sandholt; Åsa Andersson; Annelli Sandbaek; Torsten Lauritzen; Charlotta Pisinger; Daniel R Witte; Thorkild I.A. Sørensen; Oluf Pedersen; Torben Hansen

doi:10.1186/1471-2350-12-4

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

Malene Hornbak, Karina Banasik, Johanne Marie Justesen, Nikolaj Thure Krarup, Camilla Helene Sandholt, Åsa Andersson, Annelli Sandbaek, Torsten Lauritzen, Charlotta Pisinger, Daniel R Witte, Thorkild I.A. Sørensen, Oluf Pedersen, Torben Hansen

7 Citations (Scopus)

Abstract

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 ISI_Matsuda(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.

Original language	English
Journal	BMC Medical Genetics
Volume	12
Issue number	1
Pages (from-to)	4
Number of pages	8
ISSN	1471-2350
DOIs	https://doi.org/10.1186/1471-2350-12-4
Publication status	Published - 6 Jan 2011

Keywords

Former Faculty of Pharmaceutical Sciences

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1186/1471-2350-12-4

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Hornbak, M., Banasik, K., Justesen, J. M., Krarup, N. T., Sandholt, C. H., Andersson, Å., Sandbaek, A., Lauritzen, T., Pisinger, C., Witte, D. R., Sørensen, T. I. A., Pedersen, O., & Hansen, T. (2011). The minor C-allele of rs2014355 in ACADS is associated with reduced insulin release following an oral glucose load. BMC Medical Genetics, 12(1), 4. https://doi.org/10.1186/1471-2350-12-4

Hornbak, M, Banasik, K , Justesen, JM, Krarup, NT, Sandholt, CH, Andersson, Å, Sandbaek, A, Lauritzen, T, Pisinger, C, Witte, DR, Sørensen, TIA , Pedersen, O & Hansen, T 2011, 'The minor C-allele of rs2014355 in ACADS is associated with reduced insulin release following an oral glucose load', BMC Medical Genetics, vol. 12, no. 1, pp. 4. https://doi.org/10.1186/1471-2350-12-4

@article{bc461f9466a94895a9384d57b7d6ac48,

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

abstract = "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{\textregistered} 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).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.",

keywords = "Former Faculty of Pharmaceutical Sciences",

author = "Malene Hornbak and Karina Banasik and Justesen, {Johanne Marie} and Krarup, {Nikolaj Thure} and Sandholt, {Camilla Helene} and {\AA}sa Andersson and Annelli Sandbaek and Torsten Lauritzen and Charlotta Pisinger and Witte, {Daniel R} and S{\o}rensen, {Thorkild I.A.} and Oluf Pedersen and Torben Hansen",

year = "2011",

month = jan,

day = "6",

doi = "10.1186/1471-2350-12-4",

language = "English",

volume = "12",

pages = "4",

journal = "B M C Medical Genetics",

issn = "1471-2350",

publisher = "BioMed Central Ltd.",

number = "1",

}

TY - JOUR

T1 - The minor C-allele of rs2014355 in ACADS is associated with reduced insulin release following an oral glucose load

AU - Hornbak, Malene

AU - Banasik, Karina

AU - Justesen, Johanne Marie

AU - Krarup, Nikolaj Thure

AU - Sandholt, Camilla Helene

AU - Andersson, Åsa

AU - Sandbaek, Annelli

AU - Lauritzen, Torsten

AU - Pisinger, Charlotta

AU - Witte, Daniel R

AU - Sørensen, Thorkild I.A.

AU - Pedersen, Oluf

AU - Hansen, Torben

PY - 2011/1/6

Y1 - 2011/1/6

N2 - 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 (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).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.

AB - 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 (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).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.

KW - Former Faculty of Pharmaceutical Sciences

U2 - 10.1186/1471-2350-12-4

DO - 10.1186/1471-2350-12-4

M3 - Journal article

C2 - 21211036

SN - 1471-2350

VL - 12

SP - 4

JO - B M C Medical Genetics

JF - B M C Medical Genetics

IS - 1

ER -

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

Abstract

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