Familial combined hyperlipidemia (FCH) is char acterized by a familial occurrence of a multiple-type hyperlipid emia, associated with coronary risk. The latter may be related to increased levels of small, dense LDL particles that have been found to be more prone to oxidative modification. We isolated total LDL as fresh as possible from 12 normolipidemic relatives with a buoyant LDL subfraction profile (group 1), 7 normolip idemic subjects with a dense LDL subtraction profile (group 2), and 16 hyperlipidemie FCH subjects with a dense LDL subfrac tion profile (group 3). In these nonobese and normotensive men, we studied the resistance of total LDL against C u2+-oxidation in vitro. In addition, we analyzed the a-tocopherol and the coen zyme Q10 contents of LDL and determined their relation to LDL oxidizability. LDL isolated from group 3 subjects was more sus ceptible to oxidative modification than LDL from group 1 sub jects (lag time: 60.4±8.1 versus 70.4± 11.4 minutes; P<.{)5). For the combined groups, the ratio of ubiquinol-10 to polyunsaturated fatty acids in LDL, together with the basal amount of dienes in LDL, were good predictors of the rale of LDL oxidation (/i'=.73, P=.00()I). In groups 2 and 3, the redox status of coenzyme Q10 (ubiquinol-10/ubiquinone-10) and the ratio of ubiquinol-10 to a-tocopherol in LDL were reduced compared with group 1 (ƒ*<.()5). The K-value, a measure of the LDL density, correlated with the the redox status (r=.37, P

The impact of apo E polymorphism on interindividual variation in plasma lipid, lipoprotein concentrations, and LDL subfraction profiles was studied in 201 well-defined patients (88 men and 103 women) with familial combined hyperlipidemia (FCH). When corrected for the concomitant influences of age, gender and obesity, the allelic variation in the apo E gene was shown to explain a statistically significant portion of the variability in lipid and (apo)lipoprotein concentrations. Carriers of the apo e2 allele exhibited a substantially higher plasma triglyceride concentration and a lower low density lipoprotein (LDL) cholesterol level, while subjects with the apo eA allele had significant higher total plasma cholesterol and LDL cholesterol levels. In line with this observation, our FCH population was characterized by an over-representation of the apo E4 allele as compared with a Dutch standard population (x 2 = 55.2, P < 0.0001). The contribution of apo E polymorphism to trait variability was different between sexes for plasma triglyceride, VLDL cholesterol, VLDL triglycerides, and high density lipoprotein (HDL) cholesterol levels. Apo E polymorphism had no impact on chemical composition of VLDL; for LDL particles the apo el allele was associated with a lower cholesterol to protein (C/P) ratio, whereas the opposite was true for the apo s4 allele. Despite the demonstrated impact of apo E polymorphism on plasma lipids and LDL chemical composition, in all phenotypic groups a dense LDL subfraction profile predominated. Thus, apo E polymorphism contributes to the lipid phenotypic expression in FCH, whereas further evidence was obtained that a dense LDL subfraction profile is an integral feature of FCH. 126 (1996) [313][314][315][316][317][318][319][320][321][322][323][324]

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