Pharmacogenomic effect of vitamin E on kidney structure and function in transgenic mice with the haptoglobin 2-2 genotype and diabetes mellitus.

@article{Nakhoul2009PharmacogenomicEO,
  title={Pharmacogenomic effect of vitamin E on kidney structure and function in transgenic mice with the haptoglobin 2-2 genotype and diabetes mellitus.},
  author={Farid Nakhoul and Rachel Miller-Lotan and Hassoup Awad and Rabea Asleh and Kheir Jad and Nakhoul Nakhoul and Roy Asaf and Niroz Abu-saleh and Andrew P. Levy},
  journal={American journal of physiology. Renal physiology},
  year={2009},
  volume={296 4},
  pages={
          F830-8
        }
}
Polymorphic loci regulating oxidative stress are potential susceptibility genes for diabetic nephropathy (DN). Haptoglobin (Hp) is an antioxidant protein which serves to protect against oxidative stress induced by extracorpuscular hemoglobin. There are two alleles at the Hp locus, 1 and 2. The Hp 1 protein is a superior antioxidant to the Hp 2 protein. The Hp 2 allele has been associated with increased prevalence of DN and appears to be associated with a more rapid progression to end-stage… 
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References

SHOWING 1-10 OF 56 REFERENCES
Haptoglobin gene polymorphism in type 2 diabetic patients with and without nephropathy: An Egyptian study.
Genetically Determined Heterogeneity in Hemoglobin Scavenging and Susceptibility to Diabetic Cardiovascular Disease
TLDR
It is proposed that the specific interaction between diabetes, CVD, and Hp genotype is the result of the heightened urgency of rapidly clearing glycosylated Hp‐Hp complexes from the subendothelial space before they can oxidatively modify low‐ density lipoprotein to atherogenic oxidized low‐density lipop protein.
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
TLDR
Vitamin E supplementation appears to reduce cardiovascular events in individuals with DM and the Hp 2-2 genotype, a subgroup that comprises 2% to 3% of the general population.
Accelerated nephropathy in diabetic apolipoprotein e-knockout mouse: role of advanced glycation end products.
TLDR
The accelerated renal injury that was observed in diabetic apo E-KO mice was attenuated by approaches that inhibit renal AGE accumulation and were associated with less albuminuria, structural injury, macrophage infiltration, TGF-beta1, and collagen expression.
Haptoglobin Genotype Is a Determinant of Iron, Lipid Peroxidation, and Macrophage Accumulation in the Atherosclerotic Plaque
TLDR
Increased iron, lipid peroxidation and macrophage accumulation in ApoE−/− Hp 2-2 plaques suggests that the Hp genotype plays a critical role in the oxidative and inflammatory response to intraplaque hemorrhage.
Haptoglobin Genotype– and Diabetes-Dependent Differences in Iron-Mediated Oxidative Stress In Vitro and In Vivo
TLDR
Taken together, data implicate redox active iron in the increased susceptibility of individuals with the Hp 2 allele to diabetic vascular disease.
Downregulation of the Hemoglobin Scavenger Receptor in Individuals With Diabetes and the Hp 2-2 Genotype: Implications for the Response to Intraplaque Hemorrhage and Plaque Vulnerability
TLDR
An impaired hemoglobin clearance capacity in Hp 2-2 DM individuals is demonstrated and may provide the key insight explaining the increased incidence of myocardial infarction in this population.
Association between Haptoglobin Gene Variants and Diabetic Nephropathy: Haptoglobin Polymorphism in Nephropathy Susceptibility
TLDR
The results suggest that the Hp2 allele may confer susceptibility to nephropathy in patients with type 1 diabetes, similar to that found in other Western European populations.
Role of Haptoglobin Phenotype in End-Stage Kidney Disease
TLDR
The prevalence of Hp 1-1 is decreased in HD patients less than 60 years of age and may provide a protective effect against mortality in elderly patients, which may be due to a fundamental difference in the rate of renal deterioration in patients with different Hp types.
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