Sorted By Test Name - Mayo Medical Laboratories

APOE
80905
expressing more severe disease. Approximately 40% of males and 20% of females with an APOB
mutation will develop coronary artery disease. The vast majority of FDB cases are caused by a single
APOB mutation at residue 3500, resulting in a glutamine substitution for the arginine residue (R3500Q).
This common FDB mutation occurs at an estimated frequency of 1:500 individuals of European descent.
Another, less frequently occurring mutation at that same codon results in a tryptophan substitution,
R3500W, and is more prevalent in individuals of Chinese and Malay descent, but has been identified in
the Scottish population as well. The R3500W mutation is estimated to occur in approximately 2% of
ADH cases. Residue 3500 interacts with other apolipoprotein B-100 residues to induce conformational
changes necessary for apolipoprotein B-100 binding to the LDL receptor. Thus, mutations at residue 3500
lead to a reduced binding affinity of LDL for its receptor. There is a high degree of phenotypic overlap
between FDB and familial hypercholesterolemia (FH), the latter due to mutations in LDLR, which
encodes for the LDL receptor (LDLR). In general, individuals with FDB have less severe
hypercholesterolemia, fewer occurrences of tendinous xanthomas, and a lower incidence of coronary
artery disease, compared with FH. Plasma LDL cholesterol levels in patients with homozygous FDB are
similar to levels found in patients with heterozygous (rather than homozygous) FH. Identification of
APOB mutations in individuals suspected of having ADH helps to obtain a definitive diagnosis of the
disease as well as determine appropriate treatment. Therapy for FDB is aimed at lowering the plasma
levels of LDL, and both heterozygotes and homozygotes generally respond well to statins. Screening of
at-risk family members allows for effective primary prevention by instituting statin therapy and dietary
modifications at an early stage.
Useful For: Aiding in the diagnosis of familial defective apolipoprotein B-100 in individuals with
elevated untreated low-density lipoprotein cholesterol concentrations Distinguishing the diagnosis of
familial defective Apolipoprotein B-100 from other causes of hyperlipidemia, such as familial
hypercholesterolemia and familial combined hyperlipidemia Comprehensive genetic analysis for
hypercholesterolemic individuals who test negative for a mutation in the LDLR gene by sequencing
(LDLRS/81013 Familial Hypercholesterolemia, LDLR Full Gene Sequence) and/or gene dosage
(LDLM/89073 Familial Hypercholesterolemia, LDLR Large Deletion/Duplication, Molecular Analysis)
Interpretation: An interpretive report will be provided.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Whitfield AH, Barrett PHR, Van Bockxmeer FM, and Burnett JR: Lipid
disorders and mutations in the APOB gene. Clin Chem 2004;50:1725-1732 2. Innerarity TL, Mahley RW,
Weisgraber KH, et al: Familial defective apolipoprotein B100: a mutation of Apolipoprotein B that causes
hypercholesterolemia. J Lipid Res 1990;31:1337-1349 3. Soria LF, Ludwig EH, Clarke HR, et al:
Association between a specific apolipoprotein B mutation and familial defective apolipoprotein B-100.
Proc Natl Acad Sci USA 1989;86:587-591
Apolipoprotein E Genotyping, Blood
Clinical Information: Apolipoproteins are structural constituents of lipoprotein particles that
participate in lipoprotein synthesis, secretion, processing, and metabolism. Apolipoproteins have critical
roles in blood lipid metabolism. Defects in apolipoprotein E (Apo E) are responsible for familial
dysbetalipoproteinemia, or type III hyperlipoproteinemia, in which increased plasma cholesterol and
triglycerides result from impaired clearance of chylomicron and very-low-density lipoprotein (VLDL)
remnants. The human APOE gene is located on chromosome 19. The 3 common APOE alleles are
designated e2, e3, and e4, which encode the Apo E isoforms E2, E3, and E4, respectively. E3, the most
common isoform in Caucasians, shows cysteine (Cys) at amino acid position 112 and arginine (Arg) at
position 158. E2 and E4 differ from E3 by single amino acid substitutions at positions 158 and 112,
respectively (E2: Arg158->Cys; E4: Cys112->Arg). The allele frequencies for most Caucasian
populations are as follows: -e2=8% to 12% -e3=74% to 78% -e4=14% to 15% E2 and E4 are both
associated with higher plasma triglyceride concentrations. Over 90% of individuals with type III
hyperlipoproteinemia are homozygous for the e2 allele. However,