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Hypothesis—haptoglobin genotype and diabetic nephropathy

Nature Clinical Practice Nephrology volume 3, pages 339–344 (2007)Cite this article

Abstract

Vascular complications cause serious morbidity in patients with diabetes mellitus. Three such complications are nephropathy, retinopathy and accelerated atherosclerotic cardiovascular disease. There is currently scant evidence of a genetic marker that predicts which patients will have vascular complications. Oxidative stress has an important role in the development of diabetic vascular complications. Haptoglobin (Hp) is a hemoglobin-binding protein that has a major role in protecting against heme-driven oxidative stress. There are two common alleles for Hp (1 and 2) and, therefore, three common Hp genotypes: Hp 1-1, Hp 2-1, and Hp 2-2. The antioxidant protection provided by Hp is genotype-dependent; the protein encoded by Hp 1-1 provides superior antioxidant protection compared with that encoded by Hp 2-2. We have shown that diabetic individuals with Hp 2-2 are more likely to develop nephropathy, retinopathy, and cardiovascular disease than those with the Hp 2-1 or Hp 1-1 genotypes.

Key Points

  • Data support a pathogenic role for oxidative stress in vascular complications of diabetes

  • Haptoglobin is an antioxidant, hemoglobin-binding protein

  • There are two haptoglobin alleles (1 and 2) and, therefore, three possible genotypes (Hp 1-1, Hp 2-2 and Hp 2-1)

  • Small, cross-sectional studies have shown that varying susceptibility of individuals with diabetes to development of microvascular complications might be influenced by their haptoglobin genotype

  • The Hp 1-1 genotype seems to be protective against diabetic vascular complications

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Acknowledgements

FM Nakhoul is partially supported by a grant from the Abutbul Family in memory of Daniel Abutbul.

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Authors and Affiliations

  1. FM Nakhoul is Assistant Professor of Medicine, R Miller-Lotan, H Awaad and R Asleh are Research Associates, and AP Levy is Associate Professor of Medicine, all in the Faculty of Medicine, Technion, Haifa, Israel.,

    Farid M Nakhoul, Rachel Miller-Lotan, Huda Awaad, Rabea Asleh & Andrew P Levy

Authors
  1. Farid M Nakhoul
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  2. Rachel Miller-Lotan
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  3. Huda Awaad
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  4. Rabea Asleh
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Correspondence to Farid M Nakhoul.

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Competing interests

The institution at which the authors are employed has partial ownership of a patent which claims to predict susceptibility to diabetic vascular disease on the basis of the Hp genotype.

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Nakhoul, F., Miller-Lotan, R., Awaad, H. et al. Hypothesis—haptoglobin genotype and diabetic nephropathy. Nat Rev Nephrol 3, 339–344 (2007). https://doi.org/10.1038/ncpneph0467

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