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Association of genes of lipid metabolism with measures of subclinical cardiovascular disease in the Diabetes Heart Study
  1. K P Burdon1,
  2. C D Langefeld2,
  3. S R Beck2,
  4. L E Wagenknecht2,
  5. J J Carr3,
  6. B I Freedman4,
  7. D Herrington4,
  8. D W Bowden1
  1. 1Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA
  2. 2Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA
  3. 3Department of Radiology, Wake Forest University School of Medicine, Winston-Salem, NC, USA
  4. 4Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA
  1. Correspondence to:
 Donald W Bowden
 Department of Biochemistry, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA; dbowdenwfubmc.edu

Abstract

Background: Dyslipidaemia is a well known risk factor for cardiovascular disease (CVD). Lipid metabolism is affected by a range of genes and proteins. This study investigated whether some of these genes are associated with measures of subclinical CVD.

Methods: Polymorphisms of paraoxonase 1 and 2, cholesteryl ester transfer protein, hepatic lipase, and lipoprotein lipase were tested for associations with measures of subclinical CVD including carotid intima-media thickness measured by B-mode ultrasound and carotid and coronary arterial calcification measured by computed tomography. Analysis was performed in 620 European American participants in the Diabetes Heart Study, 83% of whom had type 2 diabetes mellitus. Associations of genotypes with subclinical CVD were tested by computing a series of generalised estimating equations.

Results: The Q192R variant of paraoxonase 1 and rs285 of lipoprotein lipase were associated with carotid artery calcium (p values = 0.002 and 0.005, respectively). Paraoxonase 2 S311C was associated with coronary artery calcium (p value = 0.037).

Conclusions: There is evidence for modest, but significant, association of multiple single nucleotide polymorphisms in lipid genes with measures of subclinical CVD.

  • BMI, body mass index
  • CAC, coronary artery calcification
  • CarAC, carotid artery calcification
  • CETP, cholesteryl ester transfer protein
  • CVD, cardiovascular disease
  • DHS, Diabetes Heart Study
  • IMT, intima-media thickness
  • HL, hepatic lipase
  • LPL, lipoprotein lipase
  • PON1, paraoxonase 1
  • PON2, paraoxonase 2
  • SNP, single nucleotide polymorphism
  • T2DM, type 2 diabetes mellitus
  • cardiovascular disease
  • coronary artery calcification
  • diabetes
  • genetics
  • lipid metabolism

https://doi.org/10.1136/jmg.2004.029850

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    Footnotes

    • This study was supported in part by the General Clinical Research Center of the Wake Forest University School of Medicine grant M01 RR07122, and grant NHLBI R01 HL67348 awarded to DWB. KPB was supported by an American Diabetes Association Mentor-based Fellowship.

    • Competing interests: none declared

    • Ethics approval: All protocols were approved by the institutional review board of Wake Forest University School of Medicine and all participants gave informed consent.