The minor C-allele of rs2014355 in ACADS is associated with reduced insulin release following an oral glucose load.
BMC Med Genet
; 12: 4, 2011 Jan 06.
Article
en En
| MEDLINE
| ID: mdl-21211036
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 ß-oxidation. Chronic exposure to fatty acids due to an impaired ß-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 (ß) = -3.8% (-6.3%;-1.3%), P = 0.003), reduced incremental area under the insulin curve (ß = -3.6% (-6.3%;-0.9%), P = 0.009), reduced acute insulin response (ß = -2.2% (-4.2%;0.2%), P = 0.03), and with increased insulin sensitivity ISIMatsuda (ß = 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 ß-oxidation of fatty acids.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Glucemia
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Butiril-CoA Deshidrogenasa
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Alelos
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Insulina
Tipo de estudio:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prevalence_studies
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Risk_factors_studies
Límite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
BMC Med Genet
Asunto de la revista:
GENETICA MEDICA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Dinamarca