Common variation in cholesteryl ester transfer protein: relationship of first major adverse cardiovascular events with the apolipoprotein B/apolipoprotein A-I ratio and the total cholesterol/high-density lipoprotein cholesterol ratio

J Clin Lipidol. 2013 Jan-Feb;7(1):56-64. doi: 10.1016/j.jacl.2012.05.003. Epub 2012 May 22.

Abstract

Background: The preference of the apolipoprotein (apo) B/apoA-I ratio over the total cholesterol/HDL cholesterol (TC/HDL-C) ratio in cardiovascular risk prediction is disputed. Cholesteryl ester transfer protein (CETP) is instrumental in lipoprotein remodelling and affects the cholesterol content in pro- and antiatherogenic lipoproteins relative to their major apolipoproteins. We tested the influence of common CETP variations on the strength of associations of a first major adverse cardiovascular event (MACE) with the apoB/apoA-I ratio compared with the TC/HDL-C ratio.

Methods: A prospective case-cohort study was performed (PREVEND cohort; no previous cardiovascular disease and no use of lipid-lowering drugs initially). Fasting serum TC/HDL-C, apoB/apoA-I, triglycerides, and common CETP variations (TaqIB [rs708272] and -629C>A [rs1800775] polymorphisms) were measured at baseline. The composite end point was incident MACE.

Results: A total of 532 of 6780 subjects experienced a first MACE during 10.8 years follow-up. The age- and sex-adjusted hazard ratio was 1.31 (95 % confidence interval 1.23-1.41) for the apoB/apoA-I ratio and 1.22 (95% confidence interval 1.26-1.39) for the TC/HDL-C ratio (both P < .001). These relationships were essentially similar within each TaqIB and -629C>A CETP genotype group. No interactions of the apoB/apoA-I ratio and the TC/HDL-C ratio with the TaqIB and the -629C>A CETP variations on incident MACE were observed (P > .20 for all).

Conclusion: The relationship of first MACE with the TC/HDL-C and the apoB/apoA-I ratio is not to an important extent dependent on common CETP variations. CETP variations are unlikely to affect the strength of the relationship of first MACE with the apoB/apoA-I ratio compared with the TC/HDL-C ratio.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Apolipoprotein A-I / blood*
  • Apolipoproteins B / blood*
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / genetics*
  • Cardiovascular Diseases / pathology
  • Cholesterol / blood*
  • Cholesterol Ester Transfer Proteins / genetics*
  • Cholesterol Ester Transfer Proteins / metabolism
  • Cholesterol, HDL / blood*
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Proportional Hazards Models
  • Prospective Studies

Substances

  • Apolipoprotein A-I
  • Apolipoproteins B
  • Cholesterol Ester Transfer Proteins
  • Cholesterol, HDL
  • Cholesterol