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The frequent UCP2 −866G>A polymorphism protects against insulin resistance and is associated with obesity: a study of obesity and related metabolic traits among 17 636 Danes

International Journal of Obesity volume 37, pages 175–181 (2013)Cite this article

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Abstract

CONTEXT:

Uncoupling protein 2 (UCP2) is involved in regulating ATP synthesis, generation of reactive oxygen species and glucose-stimulated insulin secretion in β-cells. Polymorphisms in UCP2 may be associated with obesity and type 2 diabetes mellitus.

OBJECTIVE:

To determine the influence of a functional UCP2 promoter polymorphism (−866G>A, rs659366) on obesity, type 2 diabetes and intermediary metabolic traits. Furthermore, to include these and previously published data in a meta-analysis of this variant with respect to its impact on obesity and type 2 diabetes.

DESIGN:

We genotyped UCP2 rs659366 in a total of 17 636 Danish individuals and established case–control studies of obese and non-obese subjects and of type 2 diabetic and glucose-tolerant subjects. Meta-analyses were made in own data set and in publicly available data sets. Quantitative traits relevant for obesity and type 2 diabetes were analysed within separate study populations.

RESULTS:

We found no consistent associations between the UCP2 −866G-allele and obesity or type 2 diabetes. Yet, a meta-analysis of data from 12 984 subjects showed an association with obesity (GA vs GG odds ratio (OR) (95% confidence interval (CI)): 0.894(0.826–0.968) P=0.00562, and AA vs GG OR(95% CI): 0.892(0.800–0.996), P=0.0415. Moreover, a meta-analysis for type 2 diabetes of 15 107 individuals showed no association. The −866G-allele was associated with elevated fasting serum insulin levels (P=0.002) and HOMA insulin resistance index (P=0.0007). Insulin sensitivity measured during intravenous glucose tolerance test in young Caucasian subjects (n=377) was decreased in carriers of the GG genotype (P=0.05).

CONCLUSIONS:

The UCP2 −866G-allele is associated with decreased insulin sensitivity in Danish subjects and is associated with obesity in a combined meta-analysis.

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Acknowledgements

This study was supported by the Danish Medical Research Council, the Danish Diabetes Association, the Gerda and Aage Haensch Foundation, the AP Møller Foundation for the Advancement of Medical Science, Novo Nordisk A/S and University of Copenhagen. Further, this work is supported by the European Commission as an integrated project under the 6th Framework Programme (LSHM-CT-2005-018734, HepAdip). The Danish Obesity Research Centre (DanORC; www.danorc.dk) is supported by the Danish Council for Strategic Research (grant 2101-06-0005). We wish to thank Annemette Forman, Tina Lorentzen and Marianne Stendal for technical assistance, AL Nielsen for data management, and Grete Lademann for secretarial support.

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  1. G Andersen and L T Dalgaard: These authors contributed equally to this work.

Authors and Affiliations

  1. Hagedorn Research Institute, Gentofte, Denmark

    G Andersen, S Anthonsen, L W Thørner, J Holmkvist, T Hansen & O Pedersen

  2. Department of Science, Systems and Models, Roskilde University, Roskilde, Denmark

    L T Dalgaard & S Anthonsen

  3. The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

    J M Justesen, T Nielsen, T Hansen & O Pedersen

  4. Steno Diabetes Center, Gentofte, Denmark

    D Witte & J O Clausen

  5. Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark

    T Jørgensen

  6. Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

    T Jørgensen & O Pedersen

  7. Department of General Practice, University of Aarhus, Aarhus, Denmark

    T Lauritzen

  8. Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark

    T Hansen

  9. Faculty of Health Sciences, University of Aarhus, Aarhus, Denmark

    O Pedersen

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Correspondence to L T Dalgaard.

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Andersen, G., Dalgaard, L., Justesen, J. et al. The frequent UCP2 −866G>A polymorphism protects against insulin resistance and is associated with obesity: a study of obesity and related metabolic traits among 17 636 Danes. Int J Obes 37, 175–181 (2013). https://doi.org/10.1038/ijo.2012.22

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