Utermann equal to 1975 first observed in the APOE polymorphism using isoelectric focusing and SDS - PAGE and can confirm that the APOE polymorphism, and subsequently confirmed by the direct detection of the cDNA sequence. three subtypes (isoform,) APOE E2, E3 and E4. Others contain only one of the major subtypes, namely homozygous; some people including the two major subtypes, that is heterozygous. Thus, the population to six different phenotypes.
Zannis in 1981, according to APOE phenotype of APOE gene model, the synthesis of APOE is located a gene locus on the three dominant alleles control, namely ε2, ε3 and ApoE ε4 each allele corresponds to a major subtype of three homozygous (E2P2, E3P3, E4P4) and three heterozygous (E2P3, E2P4, E3P4) six common phenotypes, in addition to rare subtype. Is generally believed that secondary subtype shift from the major subtypes of post-translational modification by sialic acid saccharification. APOE amino acid sequences 112 and 158 of the amino acid residues, Arg and Cys substitution determine the subtype of the type. of apo the E4 are in these two positions of Arg; of APOE2, are Cys; 112 Cys, and 158 Arg were of apo the E3 subtype, natural populations, gene frequencies of ε3 the distribution of the maximum of APOE3P3 phenotype distribution frequency about 70%. Containing the E3 heterozygotes (E4P3, E3P2) center (two and more than 20%), E2P2, E4P4 phenotype of the lowest frequency (two and no more than 8%). Frequency due of apo the E3, it is considered "wild type" of APOE2 and APOE4, which mutated from the variant receptor binding compared with wild-type decline, such as the combination of APOE2 receptor activity dropped to less than 1% of of of APOE3 activity, E2, this receptor binding decline is closely related with genetic lipid disorders.
APOE polymorphism has important biological properties, the APOE polymorphism is the current hot topic in medicine. APOE phenotype and genotype detection method, over the years has isoelectric focusing, immunoblotting, two dimensional gel electrophoresis method for testing and genetic analysis technologies. From the genetic level of APOE genotype is clearly better than the protein phenotype, because of APOE post-translational modifications may affect protein analysis, diagnosis and treatment of related diseases provides a convenient.
Of APOE, human APOE is mainly in the liver and brain tissue synthesis in other tissues, including monocytes (including macrophages), adrenal, ovarian granulosa cells can synthesize. The brain APOE mRNA expression in total liver 1P3, star-shaped nerve cells is their main synthesis site. APOE play an important role in the transport and metabolism of plasma cholesterol, triglyceride, and perform its functions mainly through interaction with the LDL receptor, VLDL receptor, LDL receptor-related protein, lipid metabolism and cardiovascular disease determinants.