The arginine rich glycoprotein apolipoprotein (apo) E protein is a 299 amino acid, of a molecular weight of 34,145 daltons (34 kDa). It is synthesized in several tissues, such as notably the liver parenchyma cells (prim generator of plasma apoE), astrocytes of the brain (major source of cerebrospinal fluid apoE) and macrophages. In plasma, apoE features on chylomicron remnants, very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL) and also on high density lipoproteins (HDL). As apoE is a crucial component of lipids, it plays an significant regulatory function in lipid metabolic process through its capacity to adhere to LDL receptors.

ApoE plays a key function in the convention catabolism of triglyceride rich lipoprotein remnants and takes part in reverse cholesterol transport and also plays a crucial role in determining interindividual differences in cholesterol levels.

In humans, the functional locus for apoE is polymorphic with 3 essential apo ε2, ε3 and ε4 alleles and several other rare allelomorphs. In population surveys, the frequencies of the apoE common alleles range from 0 to 14% for apo ε2, 48 to 91% for ε3 and 5 to 39% for ε4. These allele frequencies are significantly heterogenous among world populations. The three common codominant alleles apo ε2, ε3, and ε4 at one autosomal locus are coding for the three apo E isoforms E2, E3 and E4, respectively. The three isoforms differ in PI by a single charge unit, apo E4 being the most basic and E2, the most acidic isoform. The three isoforms E2, E3 and E4 decide the 6 apoE phenotypes in the populations: E2/2, E4/4 and E3/3 in homozygotes and E3/2, E4/2 and E4/3 in heterozygotes.

The 3 alleles ε2, ε3 and ε4 demonstrate differences in amino acid residues at 2 sites, 112 and 158 (Rall et al. 1982a). Apo ε4 has arginines and apo ε2 has cysteines at both sites, while apo ε3 has a cysteine at residue 112 and an arginine at 158. In all populations analyzed so far, apo E3 has been the prevailing isoform but the relative proportions of the three isoforms have presented variations amongst populations. The genetic variation at apoE locus and particularly the higher frequencies of ε4 allele may be a contributory factor for coronary heart disease risk. India with its social makeup is alarmingly establishing an growing curve in CHD occurrences. The genetic polymorphism at this locus in Indian populations could allow for an chance to interpret the cause of CHD risk. Some surveys were carried out on apoE polymorphism amongst European and mixed North American populations and very few studies in the remaining parts of the world.

References:
P. Venkatramana, P. Chengal Reddy and R. E. Ferrell. 2001. Apolipoprotein E Polymorphism Among the Indian Populations and its Comparison with Other Asian Populations. International Journal of Human Genetics. 183-186

A. Belkovets, S. Kurilovich M, Dolgich and Agarwal DP. 2001. Distribution of Apolipoprotein E (APOE) Genotypes in a Siberian Female Population Sample. International Journal of Human Genetics. 179-182