The Three Major APOE Human Alleles - Terminology

 

The Three Major APOE Human Alleles

 

Apo-E belongs to a family of fat-binding proteins called apolipoproteins. In the central nervous system, Apo-E is mainly produced by astrocytes and transports cholesterol to neurons^[8] via APOE receptors, which are members of the low density lipoprotein receptor gene family.^[9] Apo-E is the principal cholesterol carrier in the brain.^[10] Apo-E is required for cholesterol transportation from astrocytes to neurons.^[8] (from wiki)

 

The three major human alleles of APO-E (E4, E3, E2) arose after the primate-human split around 7.5 million years ago. These alleles are the by-product of non-synonymous mutations which led to changes in functionality. The first allele to emerge was APO-E4. (from wiki)

 

About 220,000 years ago, a cysteine to arginine substitution took place at amino acid 112 (Cys112Arg) of the APO-E4 allele, and this resulted in the E3 allele. Finally, 80,000 years ago, another arginine to cysteine substitution at amino acid 158 (Arg158Cys) of the APO-E3 allele created the E2 allele.^[15][13] (from wiki)

 

E4 allele has Cys at 112 and Arg at 158 with worldwide allele freq. = 13.7%

Polymorphism rs7412-C, rs429358-C (388C-526C)

rs429358 (C;C) is only APOE4/4

 

Substitution on APO-E4 allele 220,000 years ago was Cys112Arg resulting in:

E3 allele with Arg at 112 and Arg at 158 with worldwide allele freq. = 77.9%

Polymorphism rs7412-C, rs429358-T (or 388C>T or 388T-526C)

 

Substitution on APO-E3 allele 80,000 years ago was Arg158Cys resulting in:

E2 allele with Arg at 112 and Cys at 158 with worldwide allele freq. = 8.4%

Polymorphism rs7412-T, rs429358-T (or 526C>T or 388T-526T)

rs429358 (T;T) is APOE3/3, APOE2/3, or APOE2/2

rs7412 (T;T) is only APOE2/2 

rs7412 (C;C) is APOE4/4, APOE3/4, or APOE3/3