Apolipoprotein B Mutation Detection

Assesses for the APOB p.Arg3527Gln (R3500Q) and p.Arg3527Trp (R3500W) variants

Indications for testing:

  • Confirm a diagnosis of familial defective Apo B-100 (FDB)
  • Identify genetic etiology for inherited hypercholesterolemia
  • Screen individuals with a family history of FDB to assess risk of coronary artery disease
Related Tests
  • Not usually recommended for cardiovascular disease risk assessment
  • May be used concurrently with cholesterol/HDL-C ratio in individuals with elevated triglycerides (>200 mg/dL)
  • Acceptable non-traditional secondary cardiovascular disease risk screen for specific populations
  • May be useful in addition to LDL-C monitoring in individuals with elevated triglycerides

Apolipoprotein B (apoB) is a protein product of the APOB gene and is the main protein of chylomicrons and low density lipoproteins (LDLs). ApoB occurs in two isoforms, intestinal apoB-48 and hepatic apoB-100. APOB gene variants that induce a conformational change in the apoB-100 protein result in reduced binding of the LDL complex to its receptor. Such variants cause the heritable condition familial defective apolipoprotein B-100 (FDB), which is associated with increased risk for hypercholesterolemia and coronary artery disease (CAD). Genetic testing may be useful when the diagnosis of FDB is unclear or to identify at-risk relatives when the causative familial variant is known.

Disease Overview


  • R3500Q: occurs in 1/500-1/700 White individuals of North America and Europe
  • R3500W: described in Scottish population and in ~2% of Asian individuals with FDB
  • Up to 15% of familial hypercholesterolemia is due to FDB
  • Variants in LDLRPCSK9, or APOB genes result in indistinguishable phenotypes for hypercholesterolemia


  • Elevated cholesterol, triglycerides
  • Premature CAD





Autosomal dominant with reduced penetrance

Variants Tested

  • APOB c.10580G>A; p.Arg3527Gln (R3500Q)
  • APOB c.10579C>T; p.Arg3527Trp (R3500W)
  • ~40% of males and 20% of females heterozygous for an APOB variant will develop CAD

Test Interpretation


Analytical sensitivity/specificity: 99.9%


  • Negative: R3500W and R3500Q not detected
  • Positive: R3500W and/or R3500Q detected
    • Associated with hypercholesterolemia and increased risk for CAD
    • Homozygotes and compound heterozygotes for R3500Q/R3500W are at greater risk for CAD than heterozygotes


  • Other APOB gene variants will not be detected
  • Variants in other genes that may cause familial hypercholesterolemia are not detected
  • Diagnostic errors can occur due to rare sequence variations
  • Not recommended for asymptomatic individuals <18 years
Additional Resources