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Association of genes of lipid metabolism with measures of subclinical cardiovascular disease in the Diabetes Heart Study

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

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