Haptoglobin Types Research Articles

Alignment of human aquaporin 4 and ß-amyloid proteins may indicate involvement of ß-amyloid in brain water homeostasis and prevention of brain edema.

Alignment of human aquaporin 4 and ß-amyloid proteins may indicate involvement of ß-amyloid in brain water homeostasis and prevention of brain edema.

Alterations in acute phase proteins, hemogram and electrophoretic pattern of equine serum proteins following change of diet from forage to forage mixed with concentrate

Despite extensive studies on the relationship between diet type and its effect on equine biochemical factors, little is known about horse serum and plasma proteins following changes in diet from forage to forage mixed with concentrate. Acute phase proteins are a group of serum proteins whose concentrations increase in response to infections, inflammation, trauma, and neoplasia. Therefore, in the present study, we evaluated the serum levels of serum biomarkers, fibrinogen and total protein concentration along with the nutritional behavior of horses during diet change. For this purpose, two types of diets, including forage (first treatment) and mixture of forage with concentrate (second treatment) were used for each horse for fifteen consecutive days. Complete blood cell counts as well as serum levels of fibrinogen, haptoglobin and amyloid type A were measured before and after dietary changes. Serum fibrinogen, haptoglobin and amyloid A levels were significantly increased in horses of the second treatment group compared to horses in the first treatment group (p<0.05). There was also a statistically significant difference in the complete blood cell count due to the change of diet from forage to forage mixed with concentrate (p<0.05). It seems that changes in the natural flora of the horse's digestive tract following a change in diet can protect the animal's body against acute inflammatory and traumatic injuries.

Hp1-1 as a Genetic Marker Regulating Inflammation and the Possibility of Developing Diabetic Complications in Patients with Type 2 Diabetes-Cohort Studies.

Background: This study assessed the influence of the haptoglobin phenotype on markers regulating inflammation in patients with type 2 diabetes. Methods: The haptoglobin phenotypes, soluble form of CD163 receptor (sCD163), p53 concentrations and high mobility group box protein 1 (HMGB1), interleukin 10 (IL-10) secretion in serum were assayed via ELISA tests. In the first part of the project, patients were divided into three groups which differed by the haptoglobin phenotype, and afterwards into two groups according to the criterion of the presence or absence of cardiovascular disease. Results: Diabetic patients with haptoglobin phenotype 1-1 (Hp1-1) had a significantly higher concentration of IL-10 and sCD163 compared to haptoglobin phenotype 2-1 (Hp2-1) and haptoglobin phenotype 2-2 (Hp2-2). Moreover, diabetic patients with Hp1-1 had a significantly lower concentration of p53 and HMGB1 compared to diabetic patients with Hp2-1 and Hp2-2. The results have shown that diabetics with Hp2-1 had a significantly lower postprandial glucose level compared to diabetics with Hp2-2. Apart from that, there were no differences in the occurrence of haptoglobin variants between patients with or without cardiovascular disease. Conclusions: Our study provides new data for a relationship between the type of haptoglobin in patients with type 2 diabetes and the concentration of factors that regulate the body’s inflammation. We have shown that the Hp1-1 can serve as a genetic marker of inflammatory processes.

Evaluation of Plasma Protein Alpha 2 and Beta in the Patients of Hepatitis B and C Virus by Radial Immunodiffusion Technique (RID)

Proteins usually found in all body fluids, the proteins it is only of the blood plasma that are examined utmost frequently for diagnostic purposes. Over 100 proteins individual have a physiological mission in the plasma, plasma protein Mostly synthesize by liver, usually exclusion of protein hormones and immunoglobulins. In this study include the twenty four patients suffering from infection hepatitis C virus and twenty four patients suffering from infection hepatitis B virus. The estimation of plasma proteins alpha 2 kind are ceruloplasmin and haptoglobin and beta type is transferrin concentration by used radial immunodiffusion technique (RID). The transferrin and haptoglobin are affected, the transferrin is decline below the normal value while the haptoglobin contain the normal value. The twenty patients from each of the HCV and HBV transferrin concentration were (105 - 109) mg/dl, while ceruloplasmin (17.4 - 49.4) mg/dl and haptoglobin (71.2 - 100) mg/dl. The concentration of the last two were the normal value haptoglobin and ceruloplasmin levels that as measured in this study, Thus, it could possibly be assumed that the level of ceruloplasmin was not affected to an extent that is clinically significant. Consequently, it is justifiable to conclude that reporting blood levels of ceruloplasmin is not of clinical value to HBV and HCV patients. Furthermore, this study showed the transferrin and haptoglobin level were the marker (out of the three) that were affected in patients with HBV and HCV when its level was compared with levels in healthy individuals, it was significant and the transferrin P (0.001), haptoglobin P (0.003). The reduction in transferrin level and increase in haptoglobin found by this study may be well linked with increased serum iron levels reported in HBV and HCV patients and the level of the fibrosis liver.

Genetic Variation and Population structure: A study on four populations of Tripura, North East India

Back Ground: Genetic polymorphisms of ABO and RhD blood group and Haptoglobin (HP) types have already been widely used to understand variation and population structure. The present study attempted to understand the variation and population structure on the basis of ABO and RhD blood group polymorphisms and Haptoglobin (HP) as serum protein polymorphism of four Tibeto-Burman speaker groups considered as aboriginal tribes of Tripura. Genetic studies on populations in north-east Indian have been performed less frequently than in the other parts of India, in spite of diversity among these populations. Aims and Objective: Best of the knowledge the present study is the first attempt on the variation and population genetic structure concerning the ABO, RhD and HP polymorphism of the four endogamous populations – Tripuri, Hrangkhawl, Rupini and Kolui tribal population of Tripura.Materials and Methods: Present study consisted of four hundred (400) participants 100 each from above mentioned population groups. ABO and RhD blood groups were done by antigen-antisera agglutination test and HP types were ascertained by Polyacrylamide Gel Electrophoresis (PAGE) following standard techniques. Allele frequencies and Fst were calculated by using standard method.Results: Examination on ABO blood group revealed higher O allele among the two groups Tripuri and Hrangkhawl followed by A and B alleles. Among the other two groups, Rupini and Kolui, revealed higher A allele and B allele respectively. Higher D allele frequency in the RHD Blood group system has been found for each of the population group. On the other hand, Serum protein marker - HP types demonstrated higher HP*2 allele frequency than HP*1 alleles. Calculated very low Fst value (0.02-0.08) of three polymorphic markers (ABO, RhD and HP) were suggestive for low differentiation among these groups, indicating less admixture and prevailing endogamous nature of these population.Conclusion: Very low Fst values of three polymorphic markers were suggestive for low differentiation among these groups, indicating least admixture and prevailing endogamous nature of these population. The overall genetic difference revealed highest distance between Tripuri and Hrangkhwal and least distance between Rupini and Kolui.Asian Journal of Medical Sciences Vol.9(3) 2018 46-49

Purification of α2-macroglobulin from Cohn Fraction IV by immobilized metal affinity chromatography: A promising method for the better utilization of plasma.

As an abundant plasma protein, α2-macroglobulin (α2-M) participates widely in physiological and pathological activities including coagulation regulation, antitumor activities, and regulation of cytokines. It also presents a therapeutic potential for radiation injury. A two-step isolation method for the purification of α2-M from Cohn Fraction IV is described. This process includes a salting-out method and immobilized metal affinity chromatography. The LC-ESI-MS/MS analysis and a comparison of the amino acid composition demonstrated that the final product was α2-M. The final protein, with a purity of approximately 95% and a yield of nearly 45%, was obtained from Cohn Fraction IV regardless of plasma haptoglobin type, although all but type 1-1 have previously been considered unfavorable for α2-M preparation. The effects of temperature, pH, and methylamine on α2-M activity were evaluated to avoid activity loss during preparation and preservation. The results suggested that α2-M activity could be readily inactivated at temperatures above 50°C, at pH levels above 9.0 or below 4.0, or in the presence of methylamine. Cohn Fraction IV is usually discarded as a biological waste product in the human serum albumin production process; because the simple process developed in this study is relatively inexpensive, the preparation of α2-M from Cohn Fraction IV may better utilize human plasma, a valuable resource.

Changes in biochemical analytes in calves infected by nematode parasites in field conditions

Parasitic infections caused by nematodes are a major problem in bovines that resulting in losses in animal health and production. Thus, the aim of this study was to evaluate alterations in selected serum biochemical analytes in calves naturally infected with gastrointestinal (GI) and pulmonary nematodes without clinical signs. For this, samples of feces and blood of 86 calves were collected. Fecal egg counts (FEC) were determined using the modified McMaster technique with a sensitivity of 50 eggs per gram of feces (EPG). Positive nematode FEC was processed for coproculture using pooled samples to identify Strongylidae infective larvae (L3). First stage-larvae (L1) of Dictyocaulus viviparous were identified by a modified Baermann method. The biochemical analytes determined were: acute phase proteins such as haptoglobin and paraoxonase type 1; the enzymes acetylcholinesterase; butyrylcholinesterase; the lipid profile (triglycerides and total, HDL, and LDL-cholesterol); serum iron profile (iron and unsaturated iron-binding capacity); total protein and albumin; pancreatic profile (amylase and lipase); and minerals (phosphorus and calcium). The calves were divided into four groups according to the results of EPG and the modified Baermann method. Group 1: healthy control animals (n=16); Group 2: calves with only GI parasites (n=51): This group was sub-divided into sub-groups according to the EPG threshold: 2a—GI parasites with low EPG (n=23), and 2b—GI parasites with high EPG (n=28). Group 3: animals with only lungworms (n=5), and Group 4: calves with lung+GI parasites (n=14). The more prevalent genera in all coprocultures were: Cooperia spp., Haemonchus spp., Oesophagostomum spp., and Trichostrongylus spp. The nonparametric Kruskal–Wallis test was used to compare the groups and Dunn's post-test was used for multiple comparisons as the data was not normally distributed (P<0.05). The haptoglobin concentration increased in calves with GI and pulmonary parasites. A significant increase in acetylcholinesterase was observed in calves infected with lungworms. Cholesterol, triglycerides, HDL, and LDL concentrations decreased but lipase concentration increased in calves with GI parasites. Therefore, this paper provides an overview of the biochemical effects produced by nematode parasites in calves in field conditions. These findings in calves without any evident clinical signs of disease could provide an indication of GI parasites and lungworm infection, especially in an endemic area for these parasites.

A Review of Haptoglobin Typing Methods for Disease Association Study and Preventing Anaphylactic Transfusion Reaction

Haptoglobin, the product of the Hp gene, is a glycoprotein involved in the scavenging of free hemoglobin. Haptoglobin levels increase or decrease in response to various acquired conditions, and they are also influenced by genetic predisposition. There were 2 major alleles, Hp 1 and Hp 2, and 1 minor allele, Hp del. Many researchers have attempted to study the haptoglobin types and their association with disease; however, no definitive conclusions have been reached yet. It is reported that patients who are genetically deficient in haptoglobin are at risk of anaphylaxis against blood components containing haptoglobin. Haptoglobin genotypes also affect the reference intervals of haptoglobin levels. Many studies have attempted to establish simple and accurate typing methods. In this paper, we have broadly reviewed several methods for haptoglobin typing—phenotyping, Southern blotting, conventional PCR, real-time PCR, and loop-mediated isothermal amplification. We discuss their characteristics, clinical applications, and limitations. The phenotyping methods are time consuming and labor intensive and not designed to detect patients harboring Hp del. The rapid and robust haptoglobin genotyping may help in preventing fatal anaphylactic reactions and in establishing the relationships between the haptoglobin phenotypes and diseases.

Association between Haptoglobin Genotype Polymorphism and Type Two (2) Diabetes in Accra, Ghana

Polymorphism of the haptoglobin (Hp) gene, characterized by alleles Hp1 and Hp2, gives rise to structurally and functionally distinct Hp protein phenotypes: Hp1-1, Hp2-1, and Hp2-2. The corresponding proteins have structural and functional differences that have influence on a particular disease. For example, Hp genotype is an independent risk factor for diabetic complications. In urban Ghana, type two diabetes mellitus (T2DM) affects at least 6% of adults. The aim of this study was to assess the association between Hp genotype polymorphism in T2DM patients in Accra. The study was a case control one. A total of 100 participants, 50 T2DM patients attending the Diabetes Clinic (Korle-Bu Teaching Hospital) and 50 healthy non-diabetic controls, were involved. Plasma glucose concentration was measured by the glucose-oxidase method. Fasting blood glucose was performed on all subjects except for the individuals with a history of T2DM. Hp genotype was determined by allele specific polymerase chain reaction (PCR). PCR produced Hp genotype-specific bands for the Hp1F, Hp1S, and Hp2 alleles. Statistical analyses revealed a significant difference in the Hp genotype distribution between diabetics and non-diabetics (2 = 7.84, df = 2, p = 0.0198). Hp1-1 was the most frequent genotype among non-diabetics (58%) whilst Hp2-2 (38%) was most frequent genotype among diabetics. Majority of the diabetics were found in the Hp1S-1F and Hp2-2 genotype groups for diastolic BP (mmHg), systolic BP (mmHg) and FBG (mM). There was a strong association between DM and Hp2-2 genotype, followed by Hp2-1 (Hp1F-2 > Hp1S- 2) with the least being Hp1-1 (Hp1F-1F, Hp1S-1F, Hp1S-1S). The risk of developing diabetes among people with Hp2-2 and Hp1F-2 genotypes was high. They can therefore be used as markers for an individual developing DM.

Haptoglobin genotype and cardiovascular outcomes in diabetes mellitus — natural history of the disease and the effect of vitamin E treatment. Meta-analysis of the medical literature

BackgroundDiabetes mellitus carries a high risk for vascular events. Diabetics with different haptoglobin (Hp) types may carry different risk profiles, and may respond differently to vitamin E treatment. We aim to summarize the evidence about cardiovascular risk in diabetic patients, according to their Hp type, and the effect of vitamin E treatment on these sub-groups. MethodsWe searched MEDLINE and on-going trials' databases until February 2011; gray literature; reference lists of identified articles; and experts. Two investigators screened and selected studies that prospectively followed cardiovascular outcomes in diabetic patients with different Hp types (natural history analysis), and randomized controlled trials reporting the effect of vitamin E on cardiovascular outcomes in diabetics, in which Hp typing was performed (interventional analysis). ResultsFive and three studies, comprising 1829 and 2110 patients, were eligible for the natural history and the interventional analyses, respectively. The percentage of diabetic patients experiencing non-fatal MI, stroke, or cardiovascular death was significantly higher in the Hp 2–2 population (odds ratio (OR) 2.03 (95% confidence interval (CI) 1.46 to 2.81)). In patients with Hp 2–2 genotype, the OR for a combined endpoint was 0.66 in favor of the vitamin E treated group (95% CI 0.48 to 0.9). This effect was not shown in other Hp types. ConclusionHp type 2–2 carries a high risk of cardiovascular events in diabetic patients. A pharmacogenomic approach towards treatment of diabetic patients with vitamin E may be warranted.

Serum Proteome of Patients with Systemic Sclerosis: Molecular Analysis of Expression and Prevalence of Haptoglobin Alpha Chain Isoforms

Haptoglobin (Hpt) is an acute phase protein characterized by three major phenotypes (Hpt 1-1, Hpt 2-1 and Hpt 2-2). The Hpt 2-2 phenotype is associated with increased prevalence of various systemic diseases, including autoimmune disorders. Moreover, the Hpt 2-2 phenotype induces a shift from Th1 to Th2 response and increases fibrotic processes. On this basis, we performed serum proteomic analysis of patients with Systemic Sclerosis (SSc), a connective tissue disorder associated with Th2-type immune response and characterized by interstitial and perivascular fibrosis due to different factors (including genetic, environmental, immunological and microchimeric factors). Serum of 23 SSc outpatients patients (4 males, 19 females, mean age 54+-5.3 years) diagnosed according to the American Rheumatism Association (ARA) criteria, were considered for the proteomic analysis and compared to serum of 21 control subjects. Serum depleted of HAP was analyzed by 2-DE, and Hpt chain spots were identified by WB. The expression frequency of each Hpt α chain in SSc patients and controls was compared and quantitative analysis of spot expression (percent Vol) was performed. Above all,, our study amplifies the limited data in the literature on proteomic analysis in SSc, also confirming previous data that revealed a significant increase of haptoglobin type 2-2 and a concomitant decrease of the 1-1 phenotype in SSc patients. Moreover, our results demonstrate that c spots are more prevalent in SSc patients than in controls (91.3% vs 55.5%, p<0.05), while the expression frequency of a and b spots does not change. In patients Hpt 2-1 or Hpt 1-1 e spot is less abundant. According to our results, the c and e spots can be considered markers for SSc and thus be of use for the early diagnosis of connective tissue disorders and in establishing appropriate treatment.

Classifying Human Haptoglobin Phenotypes on Native‐PAGE Using a Modified Coomassie Brilliant Blue R 250 Staining

AbstractThere are three types of human Haptoglobin, Hp 1‐1, Hp 2‐1, and Hp 2‐2, each characterized by a distinct combination of the two α chains of the holoprotein. A modified Coomassie Brilliant Blue R 250 (mCBB‐R250) staining method for detecting the phenotypes of human blood haptoglobin molecules is presented. Addition of excess hemoglobin to the sample allowed specific formation of different haptoglobin‐hemoglobin complexes, which, in turn can be separated into distinctive migration pattern on native‐PAGE and stained by CBB‐R250. The typing results are consistent with that using Western blotting. In comparison to the existing methods for haptoglobin typing, our method is comparable in accuracy, and is easier to carry out. The results on typing of 29 plasma samples from Taipei Blood Center were also presented.

Serum haptoglobin types in patients with hemoglobinopathies

Haptoglobin types were determined in 626 individuals living in the State of São Paulo (Brazil). Of these, 484 had Hb AA, 31 major beta thalassemia, 43 minor beta thalassemia, 14 Hb SS, and 54 Hb AS. Frequency distribution of the three most common types observed among patients with type beta thalassemia differed significantly from that observed in the Caucasian group with Hb AA. There was a significant increase in Hp 1-1, which led us to assume that these disorders participate in a selective process acting on haptoglobins and altering the equilibrium of their frequencies. This relationship was not observed when we compared patients with Hb SS and Hb AS with Black patients with Hb AA, although the type most often observed among patients with Hb SS was Hp 1-1. The distributions of Hp groups observed among Caucasian and Black patients with Hb AA were similar to those obtained by other investigators for the South and Southeast regions of Brazil, with the exception of Rio de Janeiro.

Thalassaemia and haptoglobin polymorphism in Egypt.

The determination of serum haptoglobin types and their distribution in 505 “genuine” unrelated Egyptians revealed a Hp1 gene frequency of 0.34, a Hp2 gene frequency of 0.66 and a slightly higher prevalence of Hp 2-2 than of Hp 2-1. Ahaptoglobinaemia was present in 0.40 % of the examined individuals. There were no significant differences between males and females. There were 33 thalassaemia heterozygotes in the sample and these individuals were not at variance with the remainder of the sample population in respect of their serum haptoglobins.

Haptoglobin and the development of cerebral artery vasospasm after subarachnoid hemorrhage

Vasospasm is a prolonged constriction of a cerebral artery that is induced by hemoglobin after subarachnoid hemorrhage (SAH). The subarachnoid blood clot also contains the protein haptoglobin, which acts to neutralize hemoglobin. Because the haptoglobin alpha gene is dimorphic, a person can expresses only one of three types of haptoglobin (alpha1-alpha1, alpha1-alpha2, or alpha2-alpha2) depending on the alpha subunit genes he or she inherits. Each of these three haptoglobin types has different antihemoglobin activities; therefore, haptoglobin may influence the development of vasospasm differently in various patients with SAH. To determine whether SAH patients who have haptoglobin containing the alpha2 subunit would be more likely to develop vasospasm than would be SAH patients who have haptoglobin alpha1-alpha1. A total of 32 patients with Fisher Grade 3 SAH were enrolled in this study. Haptoglobin type was determined by polyacrylamide gel electrophoresis. The primary measure for vasospasm was increased blood flow velocities as detected by daily transcranial Doppler ultrasonography (TCD). The authors found that only 2 of 9 patients with haptoglobin alpha1-alpha1 (22%) had development of "possible" vasospasm as measured by TCD, whereas 20 of 23 patients with the haptoglobin alpha2 subunit (either the alpha1-alpha2 or alpha2-alpha2 haptoglobin types) had development of "possible" vasospasm (87%). The secondary measure for vasospasm was cerebral angiography performed between 3 and 14 days after SAH. Similar results (17% vs 56%) were seen between these groups in those patients who underwent cerebral angiography, although its inconsistent use limited the strength of the statistical comparison. Haptoglobins containing the alpha2 subunit seem to be associated with a higher rate of vasospasm than is haptoglobin alpha1-alpha1.

Influence of human haptoglobin polymorphism on oxidative stress induced by free hemoglobin on red blood cells

An in vitro study was conducted to determine whether haptoglobin phenotypes differed in their protective effect against oxidative stress induced by extracellular hemoglobin on red blood cells. Conjugated dienes and thiobarbituric acid-reactive substances (TBARS) were determined in human red blood cell membranes in the presence of hemoglobin and various concentrations of each type of purified haptoglobin. In addition, the release of K+ and lactate dehydrogenase from red blood cells was measured. A protective effect of haptoglobin was observed in terms of results obtained for the four parameters examined, with significant differences (p<0.001) between the three haptoglobin types; type 1-1 was the most active and type 2-2 the least active. A proportion of oxidative damage was not sensitive to haptoglobin, but to desferrioxamine (an iron chelator), indicating the participation of two actors, hemoglobin and free iron, in the oxidative stress of membrane lipids. The antioxidant role of haptoglobin and the phenotype dependence were confirmed for preventing possible oxidative damage induced by free hemoglobin and iron release during its catabolism.

Serum vitamin C concentration is influenced by haptoglobin polymorphism and iron status in Chinese

Background Vitamin C is a powerful antioxidant (free radical scavenger). Apart from the diet, other factors regulating its catabolism may affect its serum concentration. Haptoglobin (Hp) is a plasma protein participating in iron metabolism. It shows a genetic polymorphism which shows marked geographical differences. We investigated the relationship between vitamin C, iron status and haptoglobin polymorphism in Chinese men and women. Methods Iron status markers were compared according to Hp phenotypes determined by chemiluminescence detection in 110 healthy Chinese subjects. The concentration of haptoglobin was determined using an immunoturbidimetric method. Serum vitamin C was tested by a 2,4-dinitrophenylhydrazine based method. Results In Chinese, the haptoglobin phenotype distribution was 10.0% Hp 1-1, 33.6% Hp 2-1, and 56.4% Hp 2-2. In the study group, serum vitamin C concentration was associated with haptoglobin type, showing lowest values in serum from Hp 2-2 subjects in males ( p = 0.028, ANOVA). In contrast to Hp phenotype, Hp concentration did not affect vitamin C concentration. Hp 2-2 shows higher haptoglobin ( p = 0.002 (ANOVA)) than individuals with the other types. Furthermore, vitamin C was influenced by (log)ferritin levels. In Chinese, vitamin C is influenced by haptoglobin polymorphism and iron status. Conclusion The present findings support the role of non-nutritional factors in vitamin C status.

Serum Free Hemoglobin Concentrations in Healthy Individuals Are Related to Haptoglobin Type

To the Editor: Hemoglobin (Hb) is the major erythrocyte protein, and measurement of free Hb in serum can be used as a marker of hemolysis. Classically, cyanohemoglobin spectrometry and immunonephelometric methods have been used for assaying free Hb in serum (1)(2). Hb metabolism partly occurs in tissue macrophages, which can engulf senescent erythrocytes (extravascular hemolysis) or take up Hb released from ruptured erythrocytes (intravascular hemolysis) and immature erythrocytes in the bone marrow. Because of the oxidative and toxic properties of the iron-containing heme in Hb, Hb is complexed by the plasma protein haptoglobin (Hp). Hp is involved in promoting the clearance of plasma Hb because Hp strongly binds free Hb and is depleted during increased hemolysis. Hp is a positive …

The relationship between haptoglobin polymorphism and serum ceruloplasmin ferroxidase activity.

The antioxidative potential of haptoglobin is type dependent; Hp2-2 has much lower antioxidative capacity than Hp1-1 or Hp2-1. It is therefore possible that other antioxidants may compensate for decreased antioxidative capacity in Hp2-2 individuals. Haptoglobin polymorphism was correlated with ceruloplasmin ferroxidase activity in a sample population of unrelated black Jordanians. Hp2-1 was the predominant type, occurring at a frequency of 0.518 and Hp2 was the common allele, occurring at a frequency of 0.6455; no Hp0-0 individuals were observed in the sample population. In general, haptoglobin concentration was highest among Hp1 homozygotes and lowest among Hp2 homozygotes, while ceruloplasmin ferroxidase activity was highest among Hp2 homozygotes and lowest among Hp1 homozygotes. Furthermore, ceruloplasmin ferroxidase activity was higher at haptoglobin concentrations >85 mg/dl compared with that at haptoglobin concentrations of 30-85 mg/dl, which was also higher than at haptoglobin concentrations <30 mg/dl, irrespective of haptoglobin type. These results suggest that ceruloplasmin ferroxidase activity is both haptoglobin type and concentration dependent.

Haptoglobin type neither influences iron accumulation in normal subjects nor predicts clinical presentation in HFE C282Y haemochromatosis: phenotype and genotype analysis.

In the UK, 90% of patients with hereditary haemochromatosis (HH) are homozygous for HFE C282Y, as are one in 150 people in the general population. However, only a minority of these will develop clinical haemochromatosis. Iron loss modifies iron accumulation but so may other genetic factors. Haptoglobin (Hp) exists as three major types (Hp 1-1, Hp 2-1 or Hp 2-2) and binds free plasma haemoglobin. In men, Hp 2-2 has been shown to be associated with increased macrophage iron accumulation and serum ferritin concentration. Furthermore, the frequency of Hp 2-2 was shown to be increased in patients with HH. We determined Hp types by phenotyping and genotyping 265 blood donor control subjects and 173 subjects who were homozygous for HFE C282Y. The latter group included 66 blood donors lacking clinical features suggestive of haemochromatosis and without a known family history, and 68 patients presenting clinically with haemochromatosis. Hp 2-2 frequencies did not differ in control subjects and C282Y homozygotes. Hp 2-2 was not a risk factor for disease development in HH. To investigate the relationship between iron accumulation and haptoglobin type, we determined transferrin saturation and serum ferritin concentration in 192 male, first-time blood donors aged 20-40 years who lacked both HFE C282Y and H63D. Transferrin saturation and serum ferritin concentrations did not vary with Hp type.