Elsevier

Metabolism

Volume 52, Issue 12, December 2003, Pages 1564-1570
Metabolism

Preliminary report
Association of cholesteryl ester transfer protein activity and TaqIB polymorphism with lipoprotein variations in Japanese subjects

https://doi.org/10.1016/j.metabol.2003.07.011Get rights and content

Abstract

Cholesteryl ester transfer protein (CETP) facilitates the transfer of cholesteryl ester from high-density lipoprotein (HDL) to apolipoprotein (apo)B-containing lipoproteins, whereby it potentially regulates steady-state concentrations of HDL-cholesterol (HDL-C), as well as low-density lipoprotein-cholesterol (LDL-C). We performed a multicenter trial to assess the association of CETP activity with plasma lipoprotein levels in 591 Japanese subjects. Women had significantly higher CETP activity (15%) and mass (24%) compared to men. For both genders CETP activity was negatively correlated with HDL-C and HDL2-C, but positively correlated with LDL-C. B2 allele frequency in TaqIB polymorphism was 40%, with no gender difference. TaqIB genotypes were significantly associated with CETP activity and HDL-C level (both P < .001). B1B1 had the highest CETP activity and the lowest HDL-C concentrations, whereas B2B2 had the lowest CETP activity and the highest HDL-C concentrations. However, no statistically significant differences in triglycerides (TG) or LDL-C were observed across TaqIB genotypes. Multivariate analysis revealed that determinants of HDL-C were age, gender, body mass index (BMI), smoking, alcohol intake, exercise, CETP activity, and TG, and for LDL-C were BMI, age, and CETP. These data demonstrate that CETP activity is a significant determinant of HDL-C and LDL-C levels and that TaqIB CETP gene polymorphism affects CETP activity and HDL-C level in Japanese population examined.

Section snippets

Subjects

The initial study population consisted of 862 unrelated Japanese patients (524 men and 338 women) attending hospitals registered for this project. A total of 234 patients (133 men and 101 women) were excluded due to the use of drugs affecting lipid metabolism, uncontrolled diabetes mellitus (HbA1C > 8%), or liver, renal, or thyroid disease. Sixteen subjects with homozygous CETP deficiency, 18 patients with familial hypercholesterolemia, and 3 patients with chylomicronemia were excluded. After

Results

Baseline demographic and lipid parameters are summarized in Table 1. Age was well matched and average BMI was normal in both groups, but men had a significantly higher average BMI than women. Prevalence of smokers, including exsmokers, daily drinkers, CAD, and hypertension was significantly higher in men than in women. For CETP, both activity (+15%) and mass (+24%) were significantly greater in women than in men (P < .001). Despite the elevated CETP activity, women had, on average, 31% higher

Discussion

In the present study, we found an inverse correlation between CETP and HDL-C, in particular for HDL2-C, and a positive correlation between CETP and LDL-C, both in men and women. In men, apoA-I and apoA-II, major protein constituents of HDL, were also negatively correlated with CETP. The positive correlation between CETP and LDL-C agreed with most previous studies.11, 12, 15, 18 However, the negative correlation between HDL-C is a controversial finding. Both Kark et al11 and Gudnason et al12

Acknowledgements

We are indebted to Japan Tobacco Inc for materials and equipment for CETP measurement, and help with the statistical analysis.

References (36)

  • Y. Moriyama et al.

    A low prevalence of coronary heart disease among subjects with increased high-density lipoprotein cholesterol levels, including those with plasma cholesteryl ester transfer protein deficiency

    Prev Med

    (1998)
  • M. Manabe et al.

    New substrate for determination of serum lecithincholesterol acyltransferase

    J Lipid Res

    (1987)
  • J. Koizumi et al.

    Deficiency of serum cholesteryl-ester transfer activity in patients with familial hyperalphalipoproteinaemia

    Atherosclerosis

    (1985)
  • Executive summary of the the Third Report of the National Cholesterol Education Program (NECP) Expert Panel on Dectection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III)

    JAMA

    (2001)
  • A.R. Tall

    Plasma cholesteryl ester transfer protein and high-density lipoproteinsNew insights from molecular genetic studies

    J. Intern. Med

    (1995)
  • A. von Eckardstein et al.

    High density lipoproteins and arteriosclerosis. Role of cholesterol efflux and reverse cholesterol transport

    Arterioscler Thromb Vasc Biol

    (2001)
  • A. Inazu et al.

    Genetic cholesteryl ester transfer protein deficiency caused by two prevalent mutations as a major determinant of increased levels of high density lipoprotein cholesterol

    J Clin Invest

    (1994)
  • K. Ikewaki et al.

    Delayed catabolism of high density lipoprotein apolipoprotein A-I and A-II in human cholesteryl ester transfer protein deficiency

    J Clin Invest

    (1993)
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