Lipoprotein genetic determination

Lipoprotein (a) is an independent risk factor for coronary artery disease [68]. It consists of two components an LDL particle and apolipoprotein (a) which are linked by a disulfide bridge. Apo(a) reveals a genetically determined size polymorphism, resulting from a variable number of plasminogen kringle IV-type repeats [69]. Statins either do not affect Lp(a) or may even increase Lp(a) [70, 71]. In a study of 51 FH patients, treated with 40 mgd 1 pravastatin, it has been shown that the increase in Lp(a) was greatest in patients with the low molecular-weight apo(a) phenotypes [70]. 

Ma, K., Cilingiroglu, M., Otvos, J.D., Ballantyne, C.M., Marian, A. J., and Chan, L. Endothelial lipase is a major genetic determinant for high-density lipoprotein concentration, structure, and metabolism. Proc. Natl. Acad. Sci. USA,... 

C.J., and Riekind, B.M. The Collaborative Lipid Research Clinics Family Study biological and cultural determinants of familial resemblance for plasma lipids, and lipoproteins. Genet. Epidemiol., 1985,... 

Apo(a) is a protein found covalently linked to apo-BlOO in some LDL particles. Those LDL particles to which apo(a) is attached are called lipoprotein(a) oxLp(a). Plasma levels ofLp(a) correlate with increased cardiovascular disease risk in most populations, but not in African-Americans. The level of Lp(a) appears to be entirely genetically determined. The Lp(a) concentration is almost entirely related to the particular alleles of the Lp(a) gene expressed by an individual. 

Lipoprotein(a) is a genetically determined protein that has atherogenic and thrombogenic properties Contribute to postprandial lipemia... 

Lp(a) exhibits a genetic size polymorphism (MW 350-840 kDa) controlled by at least seven autosomal alleles. At the same time, these alleles are also involved in determining the plasma concentrations of the lipoprotein. 

Schultz, J. S., Shreffier, D. S., and Harvie, N. R., Genetic and antigenic studies and partial purification of human serum lipoprotein carrying the Lp antigenic determinant. Proe. Nat. Acad. Sd. U.S. 61, 963-970 (1968). 

The choice of target cells is another point worthy of discussion. In some instances, this choice is pre-determined, e.g. treatment of the genetic condition familial hypercholesterolemia would require insertion of the gene coding for the low-density lipoprotein receptor specifically in hepatocytes. 

Phylloquinone is absorbed in the proximal small intestine, by an energy-dependent mechanism, and is incorporated into chylomicrons. Estrogens increase phylloquinone absorption in both male and female animals, and male animals are more susceptible to dietary vitamin K deprivation than females (loUy et al., 1977). Even after an overnight fast, about half the plasma vitamin K is present in chylomicron remnants, and only a quarter in low-density lipoprotein. The plasma concentration of phylloquinone is associated with genetic variants of apoprotein E, which determines the binding of chylomicron remnants to the liver lipoprotein receptor (Kohlmeier et al., 1996). 

Sing CF, Davignon J (1985) Role of the apolipoprotein E polymorphism in determining normal plasma Upid and lipoprotein variation. Am J Hum Genet 37 268-285... 

The human paraoxonase-1 (PONl) is a 45kDa calcium-dependent enzyme bound to high-density lipoprotein (HDL) particles, in association with other apolipoproteins. PON 1 shows a genetic polymorphism the most prominent determines the Q192R allozyme, which can have a substantial impact on PONl activity against OPs and arylesters (Smo-len et al, 1991) (Table 70.1). The enzyme was shown to be involved in the protection against atherosclerosis (Shih... 

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