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Polymorphisms in the Selenoprotein S gene and subclinical cardiovascular disease in the Diabetes Heart Study

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Abstract

Selenoprotein S (SelS) has previously been associated with a range of inflammatory markers, particularly in the context of cardiovascular disease (CVD). The aim of this study was to examine the role of SELS genetic variants in risk for subclinical CVD and mortality in individuals with type 2 diabetes mellitus (T2DM). The association between 10 polymorphisms tagging SELS and coronary (CAC), carotid (CarCP) and abdominal aortic calcified plaque, carotid intima media thickness and other known CVD risk factors was examined in 1220 European Americans from the family-based Diabetes Heart Study. The strongest evidence of association for SELS SNPs was observed for CarCP; rs28665122 (5′ region; β = 0.329, p = 0.044), rs4965814 (intron 5; β = 0.329, p = 0.036), rs28628459 (3′ region; β = 0.331, p = 0.039) and rs7178239 (downstream; β = 0.375, p = 0.016) were all associated. In addition, rs12917258 (intron 5) was associated with CAC (β = −0.230, p = 0.032), and rs4965814, rs28628459 and rs9806366 were all associated with self-reported history of prior CVD (p = 0.020–0.043). These results suggest a potential role for the SELS region in the development subclinical CVD in this sample enriched for T2DM. Further understanding the mechanisms underpinning these relationships may prove important in predicting and managing CVD complications in T2DM.

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Acknowledgments

This study was supported in part by R01 HL67348, R01 HL09230, and R01 NS058700 to Dr Donald W Bowden. The authors thank the other investigators, the staff, and the participants of the DHS study for their valuable contributions. We would like to acknowledge the Centre for Public Health Genomics at Wake Forest University for its continued support of our biostatisticians.

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Authors and Affiliations

  1. Center for Human Genomics, Wake Forest School of Medicine, Winston-Salem, NC, USA

    Amanda. J. Cox, Allison B. Lehtinen, Jianzhao Xu & Donald W. Bowden

  2. Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC, USA

    Amanda. J. Cox, Allison B. Lehtinen, Jianzhao Xu & Donald W. Bowden

  3. Department of Biochemistry, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157, USA

    Amanda. J. Cox, Allison B. Lehtinen & Donald W. Bowden

  4. Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA

    Carl D. Langefeld

  5. Department of Internal Medicine–Nephrology, Wake Forest School of Medicine, Winston-Salem, NC, USA

    Barry I. Freedman

  6. Department of Radiologic Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA

    J. Jeffrey Carr

Authors
  1. Amanda. J. Cox
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  2. Allison B. Lehtinen
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  3. Jianzhao Xu
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  4. Carl D. Langefeld
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  5. Barry I. Freedman
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  6. J. Jeffrey Carr
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  7. Donald W. Bowden
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Corresponding author

Correspondence to Donald W. Bowden.

Additional information

Communicated by Massimo Federici.

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Cox, A.J., Lehtinen, A.B., Xu, J. et al. Polymorphisms in the Selenoprotein S gene and subclinical cardiovascular disease in the Diabetes Heart Study. Acta Diabetol 50, 391–399 (2013). https://doi.org/10.1007/s00592-012-0440-z

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  • DOI: https://doi.org/10.1007/s00592-012-0440-z

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