Atherosclerosis 152 (2000) 239 – 248 The contribution of candidate genes to the response of plasma lipids and lipoproteins to dietary challenge Yechiel Friedlander a , Eran Leitersdorf b, *, Roni Vecsler a , Harald Funke c , Jeremy Kark a a The Department of Social Medicine, The Hebrew Uniersity -Hadassah School of Public Health, Jerusalem, Israel b The Department of Medicine, Hadassah Uniersity Hospital, PO Box 12221, 91120 Jerusalem, Israel c Institute of Clinical Chemistry and Laboratory Medicine, Uniersity of Munster, Munster, Germany Received 7 June 1999; received in revised form 19 October 1999; accepted 2 November 1999 Abstract The possible role of four candidate genes in lipid and lipoprotein response to diet was examined in 214 members of two large kibbutz settlements in Israel. Four site polymorphisms (signal peptide insertion/deletion, XbaI, EcoRI and MspI) of the apo B gene, the common apo E genotypes, three common mutations (T-93G, S447stop and N291S) of the LPL gene and the CETP I405V RFLP were determined. The average reduction induced by diet in participants with the absence of the EcoRI restriction site (L4154) of the apo B gene compared with those found to be homozygotes for the restriction site (G/G4154) were: 16.2 and 8.0 mg/dl for total cholesterol (TC) (P =0.01); and 15.6 and 6.2 mg/dl for LDL-C (P =0.007), respectively. TC and LDL-C baseline levels were significantly different among the apo-E genotypes, yet there were no significant effects on lipid and lipoprotein dietary response. Triglyceride baseline values were significantly lower (P =0.007) among subjects with the LPL S447stop mutation and HDL-C was significantly lower (P =0.008) among subjects found to be heterozygous for the LPL N291S mutation. A heterogeneous response for triglyceride was observed for individuals with the S291 allele as compared to those individuals who were found to be homozygous for the N291 allele. No differences in dietary responsiveness were observed among the apo E and CETP genotypes. In conclusion, our results suggest that sequence variation(s) in the coding region of the apo B gene linked to the EcoRI polymorphism are associated with total cholesterol and LDL-C responsiveness to dietary manipulation. In our study population, LPL mutations had a significant effect on TG and HDL-C baseline levels and on their response to diet. © 2000 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Lipids; Lipoproteins; Genetics; Diet www.elsevier.com/locate/atherosclerosis 1. Introduction Levels of plasma lipids and lipoproteins can be al- tered by diet and the magnitude of dietary effects varies between individuals [1 – 4]. These differences could re- sult from different dietary adherence or may be due to true inter-individual variation in the response [1,5]. Other factors that may influence the response include sex [6], age [7], BMI [8] and the basal level of plasma lipids [9]. It is well established that genetic variation con- tributes to the basal plasma levels of lipids and lipo- proteins. Various studies have shown an association between lipid and lipoprotein levels and the apolipo- protein B (apo-B) RFLPs [10–14], however this has not been consistent [15,16]. In addition, studies have indi- cated that the apo E polymorphism influences plasma lipid levels [17]. Recent studies have shown that varia- tion at the lipoprotein lipase (LPL) and at the choles- terol ester transfer protein (CETP) loci also contribute to between-individual variation in plasma lipid and lipoprotein levels within the normal population [18 – 22]. It has been proposed that genetic variation may also contribute to the variability of these levels over time and in response to environmental exposure [23 – 26]. * Corresponding author. Tel.: +972-2-6778029; fax: +972-2- 6411136. E-mail address: eranl@hadassah.org.il (E. Leitersdorf). 0021-9150/00/$ - see front matter © 2000 Elsevier Science Ireland Ltd. All rights reserved. PII:S0021-9150(99)00474-8