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…
34 Citations
Haptoglobin Polymorphism as a Risk Factor for Chronic Kidney Disease: A Case-Control Study
- Biology, MedicineAmerican Journal of Nephrology
- 2011
It is shown that Hp2-2 genotype is an independent risk factor for CKD, together with diabetes, hypertension, hypertension and dyslipidemia.
Haptoglobin genotype and its role in determining heme-iron mediated vascular disease.
- BiologyPharmacological research
- 2012
Haptoglobin 2-2 genotype is associated with increased risk of type 2 diabetes mellitus in northern Chinese.
- BiologyGenetic testing and molecular biomarkers
- 2012
The results showed that the Hp2-2 genotype is associated with increased risk of T2DM in the northern Chinese Han population.
The Non Mineral Axis Klotho-Vitamin D in Diabetic Nephropathy: Review
- Medicine, Biology
- 2015
The aim of this review is to understand the importance of klotho protein and vitamin D in the pathogenesis of DN and as a potential future target for treatment.
Poor lysosomal membrane integrity in proximal tubule cells of haptoglobin 2-2 genotype mice with diabetes mellitus.
- Biology, MedicineFree radical biology & medicine
- 2012
Haptoglobin Genotype and Renal Function Decline in Type 1 Diabetes
- MedicineDiabetes
- 2009
Although Hp genotype is not associated with albuminuria per se, it may be an independent determinant of early renal function decline and progression to ESRD, suggesting further insight into the pathogenesis of renal disease in type 1 diabetes.
Haptoglobin genotype modifies the association between dietary vitamin C and serum ascorbic acid deficiency.
- MedicineThe American journal of clinical nutrition
- 2010
The findings suggest that the greater antioxidant capacity of Hp1 might spare serum ascorbic acid.
New Insights into the Interaction between Increased Iron-Deposition in the Kidney and Vitamin D/Klotho Axis in Diabetic Nephropathy
- Medicine, Biology
- 2016
New pathways involved in the pathogenesis of diabetic nephropathy are described to describe, including the increased production of free radicals via oxidative stress due to increased iron deposition in the lysosomes of the proximal convolute tubules.
Antioxidant, Anti-Inflammatory, and Metabolic Properties of Tocopherols and Tocotrienols: Clinical Implications for Vitamin E Supplementation in Diabetic Kidney Disease
- MedicineInternational journal of molecular sciences
- 2019
A review of the literature about the role of vitamin E supplementation on diabetic nephropathy is performed, also describing the underlying antioxidant, anti-inflammatory, and metabolic mechanisms to evaluate the possible use of tocopherols and tocotrienols in clinical practice.
Meta-analysis of the association of the haptoglobin genotype with cardiovascular outcomes and the pharmacogenomic interactions with vitamin E supplementation
- MedicinePharmacogenomics and personalized medicine
- 2018
The Hp genotype is a risk factor for CV events in patients with DM, and administration of vitamin E appears to offer a low cost and accessible means of reducing CV events and mortality in this population.
References
SHOWING 1-10 OF 56 REFERENCES
Haptoglobin gene polymorphism in type 2 diabetic patients with and without nephropathy: An Egyptian study.
- MedicineEuropean journal of internal medicine
- 2007
Genetically Determined Heterogeneity in Hemoglobin Scavenging and Susceptibility to Diabetic Cardiovascular Disease
- Biology, MedicineCirculation research
- 2003
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
- MedicineArteriosclerosis, thrombosis, and vascular biology
- 2008
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.
Application of pharmacogenomics in the prevention of diabetic cardiovascular disease: mechanistic basis and clinical evidence for utilization of the haptoglobin genotype in determining benefit from antioxidant therapy.
- Biology, MedicinePharmacology & therapeutics
- 2006
Accelerated nephropathy in diabetic apolipoprotein e-knockout mouse: role of advanced glycation end products.
- Medicine, BiologyJournal of the American Society of Nephrology : JASN
- 2004
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
- BiologyArteriosclerosis, thrombosis, and vascular biology
- 2007
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
- BiologyCirculation research
- 2005
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
- Biology, MedicineCirculation research
- 2007
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
- Medicine, BiologyNephron Experimental Nephrology
- 2007
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
- Medicine, BiologyNephron Experimental Nephrology
- 2004
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.