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Lack of association between uncoupling protein-2 Ala55Val polymorphism and incident diabetes in the atherosclerosis risk in communities study

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Abstract

Type 2 diabetes mellitus (T2DM) is characterized by impaired insulin secretion, peripheral insulin resistance, and increased hepatic glucose production. Genes that contribute to genetic susceptibility to T2DM function in numerous biochemical pathways. Uncoupling protein-2 (UCP2) functions as a negative regulator of insulin secretion. Animal studies show induction of UCP2 plays a pathogenic role in the progression of obesity-induced T2DM and some human studies have shown an association between a common UCP2 polymorphism, Ala55Val (rs660339), and T2DM, obesity, and resting metabolic rate with the Val/Val genotype conferring increased risk. We investigated the relationship between the Ala55Val variant and incidence of T2DM among 12,056 participants in the Atherosclerosis Risk in Communities (ARIC) Study aged 45–64 years at baseline. Incident T2DM (n = 1,406) cases were identified over 9 years of follow-up. The Val55 allele frequency was 44% in blacks and 41% in whites. The rate of T2DM per 1,000 person was 15.0, 15.6, and 15.6 yearsfor Ala/Ala, Ala/Val, and Val/Val genotypes, respectively. We found no significant association between UCP2 genotypes and incident T2DM in the whole cohort, in race-gender subgroups, or in categories of body mass index (normal, overweight and obese). The Ala55Val polymorphism of UCP2 was not associated with incident T2DM in the ARIC cohort.

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Acknowledgments

We are grateful for resources from the NIH Training Grant in Cardiovascular Disease Genetic Epidemiology (T32-HL007972). The ARIC Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, and N01-HC-55022. The authors thank the staff and participants of the ARIC study for their important contributions.

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Authors and Affiliations

  1. Division of Epidemiology and Community Health, University of Minnesota, 1300 South 2nd Street, Suite 300, Minneapolis, MN, 55454, USA

    Suzette J. Bielinski, James S. Pankow & Aaron R. Folsom

  2. Human Genetics Center, University of Texas-Houston Health Science Center, Houston, TX, USA

    Eric Boerwinkle

  3. Department of Pediatrics, USDA/ARS Children’s Nutrition Center, Baylor College of Medicine, Houston, TX, USA

    Molly S. Bray

  4. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    W. H. Linda Kao

Authors
  1. Suzette J. Bielinski
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  2. James S. Pankow
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  3. Eric Boerwinkle
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  4. Molly S. Bray
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  5. W. H. Linda Kao
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  6. Aaron R. Folsom
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Correspondence to Suzette J. Bielinski.

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Bielinski, S.J., Pankow, J.S., Boerwinkle, E. et al. Lack of association between uncoupling protein-2 Ala55Val polymorphism and incident diabetes in the atherosclerosis risk in communities study . Acta Diabetol 45, 179–182 (2008). https://doi.org/10.1007/s00592-008-0039-6

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  • DOI: https://doi.org/10.1007/s00592-008-0039-6

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