Variants in adiponectin signaling pathway genes show little association with subclinical CVD in the diabetes heart study

Authors

  • Amanda J. Cox,

    1. Center for Human Genomics, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
    2. Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
    3. Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
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    • Disclosure: The authors declared no conflicts of interest.

  • John E. Lambird,

    1. Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
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  • S. Sandy An,

    1. Center for Human Genomics, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
    2. Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
    3. Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
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  • Thomas C. Register,

    1. Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
    2. Department of Pathology - Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
    3. Department of Radiologic Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
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  • Carl D. Langefeld,

    1. Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
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  • J.Jeffrey Carr,

    1. Department of Radiologic Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
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  • Barry I. Freedman,

    1. Department of Internal Medicine-Nephrology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
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  • Donald W. Bowden

    Corresponding author
    1. Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
    2. Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
    • Center for Human Genomics, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
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  • Funding agencies: This study was supported in part by R01 HL67348, R01 HL09230, and R01 NS058700 to Dr Donald W Bowden.

Correspondence: Donald W Bowden (dbowden@wakehealth.edu)

Abstract

Objective

Understanding the interplay between adiposity, inflammation, and cardiovascular complications in type 2 diabetes mellitus (T2DM) remains a challenge. Signaling from adipocytes is considered important in this context. Adiponectin is the most abundant adipocytokine and has been associated with various measures of cardiovascular disease (CVD). This study examines the relationships between genetic variants in the adiponectin (ADIPOQ) and adiponectin-related signaling pathway genes and measures of subclinical CVD (vascular calcified plaque and carotid intima-media thickness), plasma lipids, and inflammation in T2DM.

Design and Methods

Single-nucleotide polymorphisms (SNPs) in ADIPOQ (n = 45), SNPs tagging ADIPOR1 (n = 6), APIPOR2 (n = 8), APPL1 (n = 6) and known rare coding variants in KNG1 (n = 3) and LYZL1 (n = 3) were genotyped in 1220 European Americans from the family-based Diabetes Heart Study. Associations between SNPs and phenotypes of interest were assessed using a variance components analysis with adjustment for age, sex, T2DM-affected status, and body mass index.

Results

There was minimal evidence of association between SNPs in the adiponectin signaling pathway genes and measures of calcified plaque; eight of the 71 SNPs showed evidence of association with subclinical CVD (P = 0.007-0.046) but not with other phenotypes examined. Nine additional SNPs were associated with at least one of the plasma lipid measures (P = 0.008-0.05).

Conclusion

Findings from this study do not support a significant role for variants in the adiponectin signaling pathway genes in contributing to risk for vascular calcification in T2DM. However, further understanding the interplay between adiposity, plasma lipids, and inflammation may prove important in the prediction and management of cardiovascular complications in T2DM.

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