title: Hypothesis--haptoglobin genotype and diabetic nephropathy.
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.
authors.affiliation: Department of Nephrology, Rambam Health Care Campus, Haifa, Israel. f_nakhoul@rambam.health.gov.il
authors.forename: Farid M
authors.initials: FM
authors.lastname: Nakhoul
authors.forename: Rachel
authors.initials: R
authors.lastname: Miller-Lotan
authors.forename: Huda
authors.initials: H
authors.lastname: Awaad
authors.forename: Rabea
authors.initials: R
authors.lastname: Asleh
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Levy
mesh_terms: D000818:Animals; D003925:Diabetic Angiopathies / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics*; D005838:Genotype; D006242:Haptoglobins / Q000235:genetics*; D006801:Humans; D018384:Oxidative Stress / Q000502:physiology
chemical_list: C485359:HP protein, human; D006242:Haptoglobins