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01.02.2012 | Article

Common variation in oxidative phosphorylation genes is not a major cause of insulin resistance or type 2 diabetes

verfasst von: L. S. Snogdal, M. Wod, N. Grarup, M. Vestmar, T. Sparsø, T. Jørgensen, T. Lauritzen, H. Beck-Nielsen, J. E. Henriksen, O. Pedersen, T. Hansen, K. Højlund

Erschienen in: Diabetologia | Ausgabe 2/2012

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Abstract

Aims/hypothesis

There is substantial evidence that mitochondrial dysfunction is linked to insulin resistance and is present in several tissues relevant to the pathogenesis of type 2 diabetes. Here, we examined whether common variation in genes involved in oxidative phosphorylation (OxPhos) contributes to type 2 diabetes susceptibility or influences diabetes-related metabolic traits.

Methods

OxPhos gene variants (n = 10) that had been nominally associated (p < 0.01) with type 2 diabetes in a recent genome-wide meta-analysis (n = 10,108) were selected for follow-up in 3,599 type 2 diabetic and 4,956 glucose-tolerant Danish individuals. A meta-analysis of these variants was performed in 11,729 type 2 diabetic patients and 43,943 non-diabetic individuals. The impact on OGTT-derived metabolic traits was evaluated in 5,869 treatment-naive individuals from the Danish Inter99 study.

Results

The minor alleles of COX10 rs9915302 (p = 0.02) and COX5B rs1466100 (p = 0.005) showed nominal association with type 2 diabetes in our Danish cohort. However, in the meta-analysis, none of the investigated variants showed a robust association with type 2 diabetes after correction for multiple testing. Among the alleles potentially associated with type 2 diabetes, none negatively influenced surrogate markers of insulin sensitivity in non-diabetic participants, while the minor alleles of UQCRC1 rs2228561 and COX10 rs10521253 showed a weak (p < 0.01 to p < 0.05) negative influence on indices of glucose-stimulated insulin secretion.

Conclusions/interpretation

We cannot rule out the possibility that common variants in or near OxPhos genes may influence beta cell function in non-diabetic individuals. However, our quantitative trait studies and a sufficiently large meta-analysis indicate that common variation in proximity to the examined OxPhos genes is not a major cause of insulin resistance or type 2 diabetes.

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Titel: Common variation in oxidative phosphorylation genes is not a major cause of insulin resistance or type 2 diabetes
verfasst von: L. S. Snogdal
M. Wod
N. Grarup
M. Vestmar
T. Sparsø
T. Jørgensen
T. Lauritzen
H. Beck-Nielsen
J. E. Henriksen
O. Pedersen
T. Hansen
K. Højlund
Publikationsdatum: 01.02.2012
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 2/2012
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-011-2377-0

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