Effect of haptoglobin on the metabolism of vitamin C

Langlois, Michel; Delanghe, Joris; Buyzere, Marc L. De; Bernard, Dirk; Ouyang, Jin

doi:10.1093/ajcn/66.3.606

Cited by 89 publications

(81 citation statements)

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“…Free Hb-driven oxidation is more effectively inhibited by Hp1 compared with Hp2, which is less efficient as a physiologic antioxidant, in vitro (7,8) and in vivo (9). A lower antioxidative potential in carriers of Hp2 may therefore contribute to the development GDM.…”

Section: Metabolic Characteristicsmentioning

confidence: 99%

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Haptoglobin Phenotype and Gestational Diabetes

et al. 2004

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OBJECTIVE -Haptoglobin (Hp), an Hb-binding plasma protein, exists in two major allelic variants. Hp1 has higher Hb binding and antioxidant capacity compared with Hp2. Individuals with Hp1 exhibit a lower incidence of angiopathies. Gestational diabetes mellitus (GDM) is an early manifestation of type 2 diabetes in pregnant women. It is usually confined to the time of gestation, but carries an increased risk to develop type 2 diabetes later in life.RESEARCH DESIGN AND METHODS -From consecutive Caucasian pregnant women (n ϭ 250) referred for oral glucose tolerance testing, the Hp phenotype was determined. Significance of distribution and odds ratios (ORs) associated with Hp phenotype were calculated for women with GDM (n ϭ 110) and women with normal glucose tolerance (n ϭ 140).RESULTS -Frequency of GDM in Hp phenotype classes increased with the number of Hp2 alleles (P Ͻ 0.001). ORs for GDM in women heterozygous and homozygous for Hp2 were 2.7 (95% CI 1.06 -6.84) and 4.2 (1.67-10.55), respectively. CONCLUSIONS -Hp phenotype is an apparent risk factor for the development of GDM in our study population. This might be due to the low antioxidative potential of Hp2 compared with Hp1. Diabetes Care 27:2103-2107, 2004H aptoglobin (Hp) is an acute-phase protein synthesized in the liver and, to some extent, in fat tissue (1) in response to interleukin 6 -type cytokines. The Hp gene is located on the long arm of chromosome 16 (16q22.3) (2). The two major Hp alleles (Hp1 and Hp2) are coding for proteins with one (Hp1) or two (Hp2) SH groups used in multimerization. The Hp1 molecule forms only dimers with a molecular weight of 86 kDa, whereas the Hp2 molecule forms multimers with a molecular weight between 170 and 900 kDa. A mixture of Hp1 and Hp2, as present in heterozygous individuals, exhibits dimeric Hp as well as oligomeric Hp, but the latter with a lower degree of polymerization than in Hp2 homozygotes. The Hp phenotype is inherited in a Mendelian pattern.Hp forms complexes with free Hb that are rapidly cleared by the liver and by macrophages. Rapid complexation of free Hb, stemming from common, low-grade intravascular hemolysis (3), is important because free Hb catalyzes the generation of reactive oxygen species, like the extremely reactive hydroxyl radical, by the so-called Fenton reaction. Reactive oxygen species promote endothelial activation and inflammation and play a crucial role in the development of endothelial dysfunction (4), which is also observed in gestational diabetes mellitus (GDM) (5). Thus Hp functions as an antioxidant and an essential vascular endothelial protector. However, the Hb-binding capacity (6) and antioxidant capacity of Hp1 is higher compared with Hp2 (7-9). The increased antioxidant function of Hp1 is thought to confer protection from angiopathies. This has been reported for coronary (10) and peripheral (11) atherosclerotic lesions, cardiac transplant vasculopathy (12), diabetic nephropathy (13), mortality in coronary heart disease (14), restenosis after peripheral and coronary angioplasty ...

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Section: Metabolic Characteristicsmentioning

confidence: 99%

“…Thus Hp functions as an antioxidant and an essential vascular endothelial protector. However, the Hb-binding capacity (6) and antioxidant capacity of Hp1 is higher compared with Hp2 (7)(8)(9). The increased antioxidant function of Hp1 is thought to confer protection from angiopathies.…”

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Haptoglobin Phenotype and Gestational Diabetes

et al. 2004

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“…Iron loading of macrophages results in iron-driven oxidative stress, which is reflected by lower serum vitamin C concentrations in Hp 2-2 subjects (Delanghe and Langlois 2002). No difference in renal threshold and urinary excretion of ascorbic acid is observed between Hp phenotypes (Langlois et al 1997).…”

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confidence: 97%

“…Hp acts to prevent the oxidative and toxic effects of the iron-containing heme in Hb (Na et al 2005). The ascorbic acid stability in body fluids is lower in Hp 2-2 individuals (Cahill and El-Sohemy 2010;Delanghe et al 2007;Sadrzadeh and Eaton 1988;Langlois et al 1997). Hp 2-2 subjects are less efficient in removing free Hb from the plasma, which may favor an iron-mediated vitamin C depletion (Langlois et al 1997;Delanghe and Langlois 2002).…”

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confidence: 99%

“…Research learns that the diet of the Inuit in the Hudson Bay (a region with a predominance of the Hp 1 allele) was mainly composed of animal sources, generally perceived as poor sources of vitamin C. It is assumed that the Inuit were able to obtain a minimum level of vitamin C (10 mg/day) from a diet of frozen/raw, fermented, and dried animal food, required to prevent scurvy (Fediuk 2000). As the stability of ascorbic acid is lower in Hp 2-2 individuals, the required daily intake of this nutrient is higher compared with the other Hp phenotypes (Cahill and El-Sohemy 2010;Delanghe et al 2007;Langlois et al 1997;Delanghe and Langlois 2002). Better tailored RDA guidelines for ascorbic acid taking into account the ethnical background could therefore contribute to a better nutritional health policy.…”

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Vitamin C deficiency: more than just a nutritional disorder

et al. 2011

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Although vitamin C deficiency and scurvy are generally considered as pure nutritional disorders, only a minority of the vitamin C concentration is determined by food intake. In the presence of transition metals (iron and copper), the antiscorbutic factor shifts from an antioxidant to a pro-oxidant function. Haptoglobin (Hp) is a plasma a-2 glycoprotein characterized by 3 common phenotypes (Hp 1-1, Hp 2-1 and Hp 2-2). Its free hemoglobin (Hb)-binding capacity prevents Hb-driven oxidative damage. When the antioxidant capacity of Hp is insufficient, its role is taken over by hemopexin (heme-binding protein) and by vitamin C (free radical scavenger). The Hp 2-2 phenotype has a lower capacity to inhibit oxidation and vitamin C depletion. In this article, two consequences of this major finding are tackled. The Hp polymorphism is an important non-nutritional modifying factor in the pathogenesis of vitamin C deficiency and scurvy, which may explain the success of long-range human migration by the natural selection of some populations characterized by high Hp 1 allele frequencies. Moreover, we propose tailoring the recommended dietary allowance (RDA) values of vitamin C, taking into consideration the Hp phenotype dependency.

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Haptoglobin

Delanghe

Langlois

2002

Wiley Encyclopedia of Molecular Medicine

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Effect of haptoglobin on the metabolism of vitamin C

Cited by 89 publications

References 22 publications

Haptoglobin Phenotype and Gestational Diabetes

Haptoglobin Phenotype and Gestational Diabetes

Vitamin C deficiency: more than just a nutritional disorder

Haptoglobin

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