Apolipoprotein B-100 Molecular Analysis, R3500Q and R3500W
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
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)
Testing Algorithm Delineates situation(s) when tests are added to the initial order. This includes reflex and additional tests.
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Polymerase Chain Reaction (PCR) Amplification with Allele-Specific Primer Extension (ASPE)
(PCR is utilized pursuant to a license agreement with Roche Molecular Systems, Inc.)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Familial Defective APOB-100
Familial Hypercholesterolemia (FH)
Familial Defective APOB-100
Familial Hypercholesterolemia (FH)
Specimen Type Describes the specimen type needed for testing
Whole Blood EDTA
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Multiple cardiovascular-related gene sequencing tests can be performed on a single specimen after a single extraction. See Multiple Cardiovascular-Related Gene Sequencing Tests in Special Instructions for a list of tests that can be ordered together.
Container/Tube: Lavender top (EDTA)
Specimen Volume: 3 mL
Collection Instructions: Send specimen in original tube.
1. The recommended assay for protein levels of apolipoprotein B is APLB/80308 Apolipoprotein B, Plasma.
2. Include physician name and phone number with the specimen.
3. Transfusions will interfere with testing for up to 4 to 6 weeks. DNA obtained from white cells may not provide useful information for patients who received a recent transfusion of blood that was not leukocyte-reduced. Wait 4 to 6 weeks until transfused cells have left the patient's circulation before drawing the patient's blood specimen for genotype testing.
1. Familial/Autosomal Dominant Hypercholesterolemia Patient Information Sheet (Supply T637) in Special Instructions
2. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (Supply T576) is available in Special Instructions.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
|Whole Blood EDTA||Ambient (preferred)|
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Autosomal dominant hypercholesterolemia (ADH) is characterized by high levels of low-density lipoprotein (LDL) cholesterol and associated with premature cardiovascular disease and myocardial infarction. The majority of ADH is caused by genetic variants that lead to decreased intracellular uptake of cholesterol. Approximately 1:500 individuals worldwide are affected by ADH and 15% of individuals with ADH have familial defective apolipoprotein B-100 (FDB) due to mutations in the LDL receptor-binding domain of the APOB gene, which maps to chromosome 2p and encodes for apolipoprotein B-100. FDB can occur in either the heterozygous or homozygous state, with the latter 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.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
An interpretive report will be provided.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This test does not detect APOB mutations other than R3500W and R3500Q.
Absence of a mutation does not preclude the diagnosis of familial defective apolipoprotein B-100 unless a specific mutation has already been identified in an affected family member.
If considering other causes of autosomal dominant hypercholesterolemia (eg, familial hypercholesterolemia), order LDLRS/81013 Familial Hypercholesterolemia, LDLR Full Gene Sequencing, or LDLM/89073 Familial Hypercholesterolemia, LDLR Large Deletion/Duplication, Molecular Analysis.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
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
Method Description Describes how the test is performed and provides a method-specific reference
Direct mutation analysis for R3500W and R3500Q is performed following PCR amplification and allele-specific, single base primer extension. (Unpublished Mayo method)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
2 months (extracted DNA only is saved)
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.
CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
81401-APOB (apolipoprotein B), common variants
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
|Result ID||Reporting Name||LOINC Code|
|89097||Reason for Referral||42349-1|