Apolipoprotein E polymorphism influences lipid phenotypic expression, but not the low density lipoprotein subfraction distribution in familial combined hyperlipidemia.
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 epsilon 2 allele exhibited a substantially higher plasma triglyceride concentration and a lower low density lipoprotein (LDL) cholesterol level, while subjects with the apo epsilon 4 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 (chi 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 epsilon 2 allele was associated with a lower cholesterol to protein (C/P) ratio, whereas the opposite was true for the apo epsilon 4 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.
Department of Medicine, University Hospital of Nijmegen, Netherlands.
S J
SJ
Bredie
J M
JM
Vogelaar
P N
PN
Demacker
A F
AF
Stalenhoef
D000483:Alleles; D001057:Apolipoproteins E / Q000235:genetics*; D002784:Cholesterol / Q000097:blood; D005260:Female; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000097:blood / Q000235:genetics*; D008055:Lipids / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood* / Q000737:chemistry; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D014280:Triglycerides / Q000097:blood
D001057:Apolipoproteins E; D008055:Lipids; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D002784:Cholesterol