| Effects of apolipoprotein and low density lipoprotein receptor gene polymorphisms on lipid metabolism, and the lipid risk factors of coronary artery disease | ||
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Apolipoprotein (apo) E is a 34-kDa protein consisting of 299 amino acids. It is a protein constituent of chylomicrons, very low density lipoproteins and HDL and VLDL remnants (Mahley 1988). On these particles, apo E serves as a ligand for uptake by lipoprotein receptors (Davignon et al. 1988, Mahley 1988,Mahley et al. 1990). Apo E is polymorphic with three common alleles: E2, E3 and E4 (Zannis et al. 1982), which are associated with variations in the blood lipid concentrations. The phenotype E2/2 is associated with type III hyperlipidemia, and E4 is associated with elevated serum total and LDL cholesterol concentrations compared to E2 and E3 (Ehnholm et al. 1986, Utermann 1987, Davignon et al. 1988). The serum concentrations of apo E are higher in individuals with E 3/3 than in individuals with E4, and highest in individuals with E2 (Berglund et al. 1993, Luc et al. 1994).
Apo E polymorphism modifies plasma lipids, at least in Caucasians, partly by affecting the efficiency of cholesterol absorption, so that individuals with E2 absorb less cholesterol than individuals with E4 (Kesäniemi et al. 1987), and individuals with the E4 allele respond better to changes in dietary cholesterol and saturated fatty acids than those without the E4 allele (Lehtimäki et al. 1995). The apo E polymorphism also modifies the metabolism of LDL. Individuals with the apo E phenotype 2/2 catabolise LDL faster than others, and normolipemic apo E 4 homozygotes catabolise LDL at a slower rate than apo E 3 homozygotes (Demant et al. 1991).
The E4 phenotype has been associated with an increased risk of CAD either directly (Kuusi et al. 1989) or via elevated atherogenic lipoprotein levels (Stuyt et al. 1991). The apo E phenotype distribution among CAD patients and myocardial infarction survivors is controversial. Some studies propose a higher frequency of apo E 4 in CAD patients (Nieminen et al. 1992, Wang et al. 1995), or myocardial infarction (AMI) survivors (Cumming and Robertson 1984), whereas others fail to detect any difference (Stuyt et al. 1991, Utermann et al. 1984).