Polymorphisms plasma protein

Data generated from metabolic clearance measurements using liver microsomes can lead to an overestimation of the tme in vivo clearance if the free versus bound fraction is not considered. A useful follow-up assay is therefore plasma protein binding measurement. The impact of cytochrome P-450 inhibition on metabolic clearance of the parent (and thus exposure) is more complicated and it remains rather difficult to make quantitative predictions from in vitro data alone. The reason is that there are generally multiple clearance pathways involved and genetic polymorphism needs to be considered as well. 

Benes P, Muzik J, Benedik J, Elbl L, Vasku A, Siskova L, Znojil V, Vacha J. The C766T low-density lipoprotein receptor related protein polymorphism and coronary artery disease, plasma lipoproteins, and longevity in the Czech population. J Mol Med 2001 79 116-120. 

Polyclonal antibodies are widely used in clinical laboratories for the measurement of plasma protein concentrations. However, immunoassays are often sensitive to the nature of the antibody used. The development of polyclonal antibodies is affected by several factors, such as the purity and dose of the antigen used, the species of host animal, and the immunization procedure. Monoclonal antibodies are viewed as a viable alternative to alleviate these problems. However, the expression of particular epitopes varies with the hpoprotein particles and among individuals in addition, the apohpoproteins themselves are polymorphic in nature. Therefore the use of a single monoclonal antibody might not detect a particular variant. If a monoclonal antibody is used in the determination of an apohpoprotein, it should he directed to an epitope that is expressed on all polymorphic forms of that particular apoprotein. Furthermore, the epitope should be equally reactive to the antibodies regardless of which hpoprotein class contains it. Alternatively a mixture of monoclonal antibodies directed at different epitopes of the apohpoprotein may also be used. Such mixtures are referred to as panmonoclonal antibodies. 

Three major alleles of the APOE gene (APOE2, APOE3, and APOE4), which codes for the plasma protein apolipoprotein E (apoE), have been studied for their associations with plasma lipoprotein concentrations. Polymorphisms in the APOE gene have been shown to influence plasma lipoprotein concentrations in carriers of certain alleles. Specifically, the E4 allele has been associated with increased LDL-C, whereas the E2 allele has been linked with lower LDL-C." Both E2 and E4 have been linked with increased plasma triglycerides."... 

Mannucci PM, Mari D, Merati G, Peyvandi F, Tagliabue L, Sacchi E, Taioli E, Sansoni P, Bertolini S, Franceschi C. Gene polymorphisms predicting high plasma levels of coagulation and fibrinolysis proteins. A study in centenarians. Arterioscler Thromb Vase Biol 1997 17 755-759. 

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