Haptoglobin genotype and its role in determining heme-iron mediated vascular disease

Goldenstein, Hagit; Levy, Nina S.; Levy, Andrew P.

doi:10.1016/j.phrs.2012.02.011

Cited by 55 publications

(52 citation statements)

References 38 publications

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“…We and others have speculated that free Hb would be the major instigator of CV through a multifactorial mechanism involving the generation of reactive intermediates that cause endothelial cell damage, depletion of the vasodilator nitric oxide, and proliferation of smooth muscle cells, a combination that ultimately leads to sustained vasoconstriction and DCI (5)(6)(7)16). In a phenotype-dependent manner, the redox potential and clearance of Hb is directly reduced and improved by Hp, respectively, where the Hp2-2 protein has been suggested to have less overall protective abilities (9)(10)(11)(17)(18)(19).…”

Section: Discussionmentioning

confidence: 99%

Haptoglobin phenotype predicts the development of focal and global cerebral vasospasm and may influence outcomes after aneurysmal subarachnoid hemorrhage

Leclerc

Blackburn

Neal

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Cerebral vasospasm (CV) and the resulting delayed cerebral ischemia (DCI) significantly contribute to poor outcomes following aneurysmal subarachnoid hemorrhage (aSAH). Free hemoglobin (Hb) within the subarachnoid space has been implicated in the pathogenesis of CV. Haptoglobin (Hp) binds free pro-oxidant Hb, thereby modulating its harmful effects. Humans can be of three Hp phenotypes: Hp1-1, Hp2-1, or Hp2-2. In several disease states, the Hp2-2 protein has been associated with reduced ability to protect against toxic free Hb. We hypothesized that individuals with the Hp2-2 phenotype would have more CV, DCI, mortality, and worse functional outcomes after aSAH. In a sample of 74 aSAH patients, Hp2-2 phenotype was significantly associated with increased focal moderate (P = 0.014) and severe (P = 0.008) CV and more global CV (P = 0.014) after controlling for covariates. Strong trends toward increased mortality (P = 0.079) and worse functional outcomes were seen for the Hp2-2 patients with modified Rankin scale at 6 wk (P = 0.076) and at 1 y (P = 0.051) and with Glasgow Outcome Scale Extended at discharge (P = 0.091) and at 1 y (P = 0.055). In conclusion, Hp2-2 phenotype is an independent risk factor for the development of both focal and global CV and also predicts poor functional outcomes and mortality after aSAH. Hp phenotyping may serve as a clinically useful tool in the critical care management of aSAH patients by allowing for early prediction of those patients who require increased vigilance due to their inherent genetic risk for the development of CV and resulting DCI and poor outcomes.

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Section: Discussionmentioning

confidence: 99%

Haptoglobin phenotype predicts the development of focal and global cerebral vasospasm and may influence outcomes after aneurysmal subarachnoid hemorrhage

Leclerc

Blackburn

Neal

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…No such benefit was observed in patients with other haptoglobin genotypes. Given that up to 40% of the European population and 90% of the Indian population carry this polymorphism (haptoglobin 2-2) [11,12], the potential of this discovery is of great significance for the care of diabetic patients.…”

Section: Editorialmentioning

confidence: 99%

Understanding the Genome: Implications for Human Nutrition?

Troesch¹,

Hoeft²

2014

Vitam Miner

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“…Hp polymorphism was shown to heavily bear on the prevalence of many diseases. Hp2-2 is over-represented in autoimmunity (16,17); it is also a risk factor in some oxidative stress-related disease states like chronic renal failure (18). Hp2 homozygosity in diabetics has been shown to increase the risk for nephropathy and retinopathy (19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

The Relationship between Haptoglobin Polymorphism and Oxidative Stress in Hemodialysis Patients

Hamad¹,

Awadallah²,

Nasr³

2013

Journal of Medical Biochemistry

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Summary Background: The relationship between haptoglobin polymorphism and oxidative stress in hemodialysis patients is not fully understood. In this study, total antioxidant capacity and ce ru - loplasmin ferroxidase activity were evaluated in relation to haptoglobin phenotype distribution in hemodialysis patients. Methods: Serum samples collected from 161 patients and 84 healthy controls were haptoglobin-typed by electrophoresis. Ceruloplasmin ferroxidase activity and total antioxidant capacity were assayed using colorimetric methods. Results: Irrespective of the haptoglobin phenotype, patients exhibited significantly lower total antioxidant capacity (1.42± 0.29 vs. 1.55±0.28 mmol/L, P=0.002) and higher ferroxidase activity than controls. Frequency of Hp1-1 and Hp2-1 in patients was 15.5% and 36% as compared with 9.5% and 41.7% in controls. While ferroxidase activity was lower in Hp2-2 patients than in controls (142±61 vs. 179±47 U/L, P=0.002), it was higher in Hp2-1 (173±56 U/L) and Hp1-1 (170±54 U/L) patients than in controls (141±43 and 99±30 U/L respectively) (P=0.002 and 0.009). Ferroxidase activity in Hp2-2 patients was significantly lower than that of Hp2-1 or Hp1-1 patients (P=0.004 and 0.034). Total antioxidant capacity was significantly lower only in Hp2-2 patients (1.44±0.25) compared to that in Hp2-2 controls (1.65±0.22) (P=0.000). Conclusions:These findings suggest that haptoglobin polymorphism can differentially impact oxidative stress levels in hemodialysis patients.

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Haptoglobin genotype and its role in determining heme-iron mediated vascular disease

Cited by 55 publications

References 38 publications

Haptoglobin phenotype predicts the development of focal and global cerebral vasospasm and may influence outcomes after aneurysmal subarachnoid hemorrhage

Haptoglobin phenotype predicts the development of focal and global cerebral vasospasm and may influence outcomes after aneurysmal subarachnoid hemorrhage

Understanding the Genome: Implications for Human Nutrition?

The Relationship between Haptoglobin Polymorphism and Oxidative Stress in Hemodialysis Patients

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