Abstract
We have developed a hypothesis to explain the association of the different binding-defective apolipoprotein E (apo-E) mutants with either the dominant or recessive mode of inheritance of type III hyperlipoproteinemia (type III HLP). The apo-E2(158 Arg → Cys) mutant is the only variant proven to be associated with recessive expression of type III HLP, and the only one for which modulation of receptor binding of the intact protein has been demonstrated. Thus, the ability of this mutant to assume either a receptor-binding-inactive or -active conformation is the key factor that determines recessive expression of type in HLP. In six other, rare apo-E variants the defective binding cannot be modulated, and we believe that this resistance to modulation causes dominant expression of type III HLP. Although recessive expression of type III HLP is much more common than dominant expression in the human population because of the much higher frequency of the apo-E2(158 Arg → Cys) allele, recessive expression may be the exception rather than the rule for the mode of inheritance of type III HLP because of the unique properties of the apo-E2(158 Arg → Cys) variant.
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Rall, S.C., Innerarity, T.L., Weisgraber, K.H., Wardell, M.R., Mahley, R.W. (1990). The type of mutation in apolipoprotein E determines whether type III hyperlipoproteinemia is expressed as a dominant or recessive trait. In: Descovich, G., Gaddi, A., Magri, G., Lenzi, S. (eds) Atherosclerosis and Cardiovascular Disease. Springer, Dordrecht. https://doi.org/10.1007/978-94-009-0731-7_10
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DOI: https://doi.org/10.1007/978-94-009-0731-7_10
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