Apolipoprotein E R112; R251G: a carboxy-terminal variant found in patients with hyperlipidemia and coronary heart disease.

Article Details

Citation

Kang AK, Jenkins DJ, Wolever TM, Huff MW, Maguire GF, Connelly PW, Hegele RA

Apolipoprotein E R112; R251G: a carboxy-terminal variant found in patients with hyperlipidemia and coronary heart disease.

Mutat Res. 1997 Sep;382(1-2):57-65.

PubMed ID
9360638 [ View in PubMed
]
Abstract

A 49 year-old hypercholesterolemic male with marked electrocardiographic ST segment depression on exercise testing was found to have an apo E E3/3 phenotype by isoelectric focusing, but an APOE E4/3 genotype using HhaI restriction isotyping. DNA sequence analysis of the proband's APOE gene found a G-->C point mutation at codon 251. This predicted a change in the amino acid encoded by codon 251, from arginine to glycine. The mutation occurred on an allele that encoded arginine at position 112 and this variant was named APOE R112; R251G. The R251G change altered a recognition site for the endonuclease StuI and was the basis for a restriction isotyping method to rapidly screen for this mutation. In relatives of the proband, APOE R112; R251G was consistently found in subjects with both hyperlipidemia and atherosclerosis. Apo E R112; R251G-containing very low density lipoproteins bound normally to macrophages in vitro. However, the proband had an abnormal post-prandial lipoprotein response to a dietary fat challenge. The association of APOE R112; R251G with abnormal phenotypes suggests that the amino acid change in the carboxy-terminal, perhaps in combination with the common amino acid polymorphism at codon 112, has a functional impact upon lipoprotein metabolism in members of this family.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Apolipoprotein EP02649Details