Introduction Directory UMM :Data Elmu:jurnal:A:Atherosclerosis:Vol152.Issue2.Oct2000:

Atherosclerosis 152 2000 327 – 336 Variants in the cholesterol ester transfer protein and lipoprotein lipase genes are predictors of plasma cholesterol response to dietary change Alison J. Wallace a , Jim I. Mann a, , Wayne H.F. Sutherland b , Sheila Williams c , Alexandra Chisholm a , C. Murray Skeaff a , Vilmundur Gudnason d , Philippa J. Talmud d , Steve E. Humphries d a Department of Human Nutrition, PO Box 56 , Room 7 n 8 , Science II Building, Union Street, Uni6ersity of Otago, Dunedin, New Zealand b Department of Medicine, Uni6ersity of Otago, PO Box 56 , Dunedin, New Zealand c Department of Pre6enti6e and Social Medicine, Uni6ersity of Otago, PO Box 56 , Dunedin, New Zealand d Department of Medicine, Uni6ersity College London Medical School, Rayne Institute, 5 Uni6ersity St., London WC 1 E 6 JJ, UK Received 15 June 1999; received in revised form 8 November 1999; accepted 6 December 1999 Abstract There are no definitive explanations as to why individuals with hypercholesterolemia, a major cardiovascular risk factor, respond differently to dietary change. Fifty five free-living individuals completed a double crossover trial with two dietary regimens, a high saturated fat diet providing 21 energy from saturated fat and 3 energy from polyunsaturated fat and a high polyunsaturated fat diet providing 11 energy as saturated fat and 10 energy as polyunsaturated fat, each phase continuing for 4 weeks. Extensive genotyping and several measures of dietary compliance have provided further insights regarding the determinants of extent of cholesterol response to changes in the nature of dietary fat. Individuals with the CETP B1B1 genotype and the LPL X447 + allele showed an average 0.44 95 CI: 0.22, 0.66 and 0.45 95 CI: 0.18, 0.72 mmoll greater change in total cholesterol, respectively, than those with one or more CETP B2 allele or homozygous for the LPL S447 allele when comparing diets high and low in saturated fat. Indices of dietary compliance including changes in reported saturated and polyunsaturated fat intake and change in triglyceride linoleate were not significantly different between the CETP genotypes. Change in reported saturated r = 0.36, P = 0.04 and polyunsaturated r = 0.22, P = 0.05 fat intake and change in triglyceride linoleate reflecting polyunsaturated fat intake r = 0.21, P = 0.07, also predicted total cholesterol response to dietary fat changes. In multivariate analyses, variation in the cholesterol ester transfer protein and lipoprotein lipase genes predicted response independent of measures of dietary compliance, suggesting that these two genes are important determinants of variation in cholesterol response to dietary change in free-living individuals. © 2000 Elsevier Science Ireland Ltd. All rights reserved. Keywords : Dietary response; Genetics; Cholesterol; Hypercholesterolemia www.elsevier.comlocateatherosclerosis

1. Introduction

Predictable changes in total and low-density lipo- protein cholesterol occur when groups of people change the nature of dietary fat [1]. Several studies have shown considerable individual variation in response to diets differing in nature and amount of fat [2 – 9]. Informa- tion relating to determinants of the extent of individual response to dietary change is relatively sparse. Male gender, older age, high body mass index, a predomi- nance of small dense LDL particles and high levels of total cholesterol, triglycerides, apolipoprotein apo B and cholesterol ester transfer CET activity are charac- teristics that have been associated with relatively large changes in plasma total cholesterol levels when nature of dietary fatty acids changes [2,4,6,10]. People with the apo E4E4 or apo E4E3 genotype also appear to be more responsive to changes in the quality of dietary fat than those who have other apoE genotypes [11 – 13]. In Corresponding author. Tel.: + 64-3-4797959; fax: + 64-3- 4797958. E-mail address : jim.mannstonebow.otago.ac.nz J.I. Mann. 0021-915000 - see front matter © 2000 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 0 2 1 - 9 1 5 0 9 9 0 0 4 9 0 - 6 addition, polymorphisms of the apoB, apoC, apoA-IV and lipoprotein lipase LPL genes have been related to the extent of cholesterol response [14 – 18], though fewer data are available and the findings are less consistent than those relating to the apoE genotypes. We report here on predictors of plasma total cholesterol change in a group of 55 individuals during four dietary periods of high or low saturated fat intake. More extensive geno- typing than had been undertaken previously in a single study has enabled analysis of the extent to which a range of polymorphisms contribute to variation in cholesterol response to alterations in the nature of dietary fat in free-living individuals. Particular attention was paid to effects of variation in the cholesterol ester transfer protein CETP and LPL genes as plasma CET activity and the LPL HindIII polymorphisms were as- sociated with response of plasma cholesterol to changes in the type of dietary fat in our earlier study [4,18]. It was also possible to estimate the effect of compliance to dietary advice on variation in response among free living individuals.

2. Methods