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  • Lab Values
  • Clinical Significance
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Test Code 887

Test Details

Haptoglobin Genotype Test

This test identifies individuals with diabetes or advanced kidney disease who may benefit from vitamin E supplementation. Those individuals with the haptoglobin 2/2 variant (35-40% of patients) are at risk for accelerated oxidative damage due to delayed clearance of haptoglobin-hemoglobin complexes. Vitamin E supplementation (400 IU daily) in those individuals has been demonstrated to reduce the risk of CVD events and CVD death.


Real time polymerase chain reaction (PCR)

Patient Preparation


Preferred Specimen

1.0 mL whole blood collected in EDTA (Lavender Top)

Alternate Specimen

Dried Blood collected on an AdvanceDx 100 card

Transport Temperature

Refrigerated (ship on frozen cold packs)


Refrigerated: 14 days

Lab Values

Lab Values

Haptoglobin Genotype Test


  • Genotype 1/1
  • Genotype 1/2

Increased risk

  • Genotype 2/2
Test Details
Clinical Significance

Clinical Significance

Haptoglobin Genotype Test

    Haptoglobin is an acute-phase protein that binds or scavenges free hemoglobin. Haptoglobin inhibits oxidative damage to end organs and prevents heme-iron loss via the kidneys by binding free hemoglobin.

  • The human Haptoglobin gene is polymorphic with two main alleles, Haptoglobin allele 1 (Hp1) and Haptoglobin allele 2 (Hp2). There are three genotypes: Hp 1/1, Hp 1/2, and Hp 2/2. 35-40% of patients have the Hp 2/2 genotype.
  • In patients with diabetes and/or kidney disease who have the Hp 2/2 variant, clearance of hemoglobin-haptoglobin complexes is delayed thereby accelerating oxidative damage and increasing the risk of CVD.
  • In a meta-analysis of 13 studies in patients with diabetes, the risk of CVD events was approximately 44% higher in those with the Hp 2/2 variant compared to those with the Hp 1/1 or 1/2 variant.


  1.  Maeda N, Yang F, Barnett DR, Bowman BH, Smithies O. Duplication within the haptoglobin Hp2 gene. Nature 1984;309:131–5.
  2. Levy AP, Asleh R, Blum S, Levy NS, Miller-Lotan R, Kalet-Litman S, et al. Haptoglobin: basic and clinical aspects. Antioxid Redox Signal 2010;12:293–304.
  3. Renner W, Jahrbacher R, Marx-Neuhold E, Tischler S, Zulus B. A novel exonuclease (TaqMan) assay for rapid haptoglobin genotyping. Clin Chem Lab Med 2016;54: 781–783.
  4. Vardi M, Levy NS, Levy AP. Vitamin E in the prevention of cardiovascular disease: the importance of proper patient selection. J. Lipid Res. 2013. 54: 2307–2314.
  5. Cahill LE, Levy AP, Chiuve SE, et al. Haptoglobin genotype is a consistent marker of coronary heart disease risk among individuals with elevated glycosylated hemoglobin. J Am Coll Cardiol 2013; 61:728–37.
  6. Cahill LE, Jensen MK, Chiuve SE, Shalom H, Pai JK, Flint AJ, Mukamal KJ, Rexrode KM, Levy AP, Rimm EB. The risk of coronary heart disease associated with glycosylated hemoglobin of 6.5% or greater is
    pronounced in the Haptoglobin 2-2 Genotype. J Am Coll. Cardiol 2015; 66:1791-9. RACT
  7. Alshiek JA, Dayan L, Asleh R, Blum S, Levy AP, Jacon G. Anti-oxidative treatment with vitamin E improves peripheral vascular function in patients with diabetes mellitus and Haptoglobin 2-2 genotype: A
    double-blinded cross-over study. Diabetes Research and Clinical Practice 2017;131:200-207.
  8. Hochberg I, Berinstein EM, Milman U, Shapira C, Levy AP. Interaction Between the Haptoglobin Genotype and Vitamin E on Cardiovascular Disease in Diabetes. Curr Diab Rep 2017;1:17-42.
  9. Milman U., et al. Vitamin E supplementation reduces cardiovascular events in a subgroup of middle-aged individuals with both type 2 diabetes mellitus and the haptoglobin 2-2 genotype: a prospective double-
    blinded clinical trial. Arterioscler Thromb Vasc Biol. 2008 Feb;28(2):341-7
  10. Asleh R, et al. Meta-analysis of the association of the haptoglobin genotype with cardiovascular outcomes and the pharmacogenomic interactions with vitamin E supplementation. Pharmgenomics Pers Med.
Lab Values
Treatment Options

Treatment Options

Haptoglobin Genotype Test

Patients with an Hp 2/2 genotype who have diabetes or kidney disease are at a significantly higher CVD risk which may be reduced by treatment with 400 IU (268 mg) of natural source vitamin E (d-alpha tocopherol) taken daily after a meal.


In a meta-analyis of 3 randomized, placebo- controlled trials, patients with Hp 2/2 variant who received vitamin E had 34% lower risk of CVD events and 53% lower risk of CVD death compared to the placebo group.1


  1. Asleh R, et al. Meta-analysis of the association of the haptoglobin genotype with cardiovascular outcomes and the pharmacogenomic interactions with vitamin E supplementation. Pharmgenomics Pers Med. 2018;11:71-82.
Clinical Significance