Genetic diseases APOE gene

Apo E consists of 299 amino acids. A genetic disease, called type 111 hyperlipoproteinemia, results from naturally occurring mutations in the apo E gene. The disease results in high plasma cholesterol, high plasma TCs, premature atherosclerosis, and xanthomas. Xanthomas arc lumpy accumulations of choles terol in the wrists, elbows, knees, and other parts of the body. The most common mutation is one that results in the conversion of Arg 158 to Cys 158 (Lohse el al., 1991). Other naturally crecurring mutations result in a truncated polypeptide, or in the complete absence of apo E,... 

There are special genetic risk factors for Alzheimer s disease - such as, for instance, the e4 allele of the apolipoprotein E (APOE) gene, isotonic variation in CYP46, CYP46 C - that significantly increase the risk of Alzheimer s disease development (Bookheimer et al. 2000 Borroni et al. 2004). Accordingly, it seems reasonable to assume that the majority of those who precipitate the disease are carriers of risk factors. 

Fig. 10.8 Absolute genetic variation (AGV) and relative genetic variation (RGV) between Alzheimer s disease and vascular dementia associated with bigenic, trigenic, and tetragenic clusters of Alzheimer s disease (AD)-related genes. APOE, apolipoprotein E PS, presenilin. (Adapted from refs. 12,19,20, and 59.)...

Some people with elevated lipoprotein levels have VLDL that migrates on electrophoresis in the (3 band rather than the pre-(3 band (see Box 2-A). The presence of the (3-VLDL is associated with a high incidence of artery disease,218 which is most likely to develop in persons homozygous for a genetic variant of apolipoprotein E. The problem may arise because apo-E is required for receptor-mediated uptake of VLDL, which interacts both with tissue LDL receptors and with hepatic apo-E receptors. Genes for many of the... 

An apolipoprotein E variant is the only unequivocal genetic risk factor for late-onset Alzheimer s disease in a variety of ethnic groups. Caucasians and Japanese with the apo-E-s4 isoform have between 10 and 30 times the risk of developing Alzheimer s by 75 years of age. While the exact mechanism is unknown, evidence suggests an interaction with amyloid. Alzheimer s disease is characterised by plaques consisting of the peptide beta-amyloid. Apolipoprotein E enhances proteolytic breakdown of this peptide. However, the isoform apo-E-e4 is much less effective, which might result in an increased vulnerability to Alzheimer s in individuals with that gene variation. 

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