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Relationship of haptoglobin polymorphism to malaria in the Solomon Islands.

Haptoglobin (Hp) polymorphism and its relationship to malaria infections was examined in Solomon Islanders under 25 years of age. The slide positive rate for malaria was 48% (53/111): Plasmodium vivax (Pv) 21 cases, Plasmodium falciparum (Pf) 16 cases and the remaining 16 were a mixture of Pv/Pf/P. malariae. Of 111 subjects examined, 17% (19 subjects) were ahaptoglobinemic (HpO). No association was observed between HpO and parasitemia, gender, anemia, serum insulin-like growth factor-1 (IGF-1) level, blood glucose level and enlargement of the spleen. These results suggest that malaria may not be the major cause of HpO in the people of the Solomon Islands.

Adolescent↗

Haptoglobin polymorphism predicts 30-day mortality and heart failure in patients with diabetes and acute myocardial infarction.

Patients with diabetes presenting with acute myocardial infarction (AMI) have an increased rate of death and heart failure. Patients with diabetes homozygous for the haptoglobin (Hp) 1 allele (Hp 1-1) develop fewer vascular complications. We tested the hypothesis that Hp type is related to the outcome of patients with diabetes presenting with AMI. We prospectively assessed the relationship between Hp type and 30-day mortality and heart failure in 1,437 patients with AMI (506 with diabetes). Multivariate logistic regression identified a significant interaction between Hp type and diabetes status on these outcome measures. Hp type was not related to outcome among patients without diabetes. In contrast, Hp 1-1 was associated with a strong protective effect with regard to the primary end point of death (OR 0.14, P = 0.015) and for death and heart failure (OR 0.35; 95% CI 0.15-0.86, P = 0.018) among patients with diabetes. Finally, among patients with diabetes, Hp 1-1 was associated with smaller infarct size. This study demonstrates that in patients with diabetes and AMI, the Hp type is an important determinant of clinical outcome and infarct size.

Diabetes Mellitus↗

Haptoglobin genotype is predictive of major adverse cardiac events in the 1-year period after percutaneous transluminal coronary angioplasty in individuals with diabetes.

OBJECTIVE: The goal of this study was to determine whether the haptoglobin (Hp) genotype was predictive of restenosis and major adverse cardiac events (MACEs) after percutaneous transluminal coronary angioplasty (PTCA) in individuals with diabetes. RESEARCH DESIGN AND METHODS: A consecutive series of 935 diabetic patients treated with oral agents and/or insulin were followed for 1 year after PTCA. The primary study end point was angiographic restenosis, MACEs and secondary study end points were defined as target vessel revascularization, myocardial infarction, and death. Two alleles exist at the Hp gene locus, denoted 1 and 2. The Hp genotype (Hp 1-1, Hp 2-1, or Hp 2-2) was determined by PCR. RESULTS: In multivariate analysis controlling for all known determinants of outcome after PTCA, we found that the Hp genotype was a highly significant independent predictor of MACEs in the 1-year period after PTCA in individuals with diabetes. This was predominantly due to differences in the risk of myocardial infarction during that period: Hp 1-1, 0 of 129 (0%); Hp 2-1, 20 of 424 (4.7%); and Hp 2-2, 32 of 382 (8.4%); P < 0.0001. CONCLUSIONS: The Hp genotype seems to be highly predictive of adverse cardiac events, particularly myocardial infarction, in the 1-year period after PTCA. Determination of the Hp genotype may be useful in the evaluation of new therapies to reduce cardiovascular risk after PTCA.

Aged↗

Haptoglobin phenotype and gestational diabetes.

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 = 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 = 110) and women with normal glucose tolerance (n = 140). RESULTS: -Frequency of GDM in Hp phenotype classes increased with the number of Hp2 alleles (P < 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.

Adult↗

Tumor necrosis factor-alpha, interleukin-6, serum amyloid A, haptoglobin, and cortisol concentrations in sows following intramammary inoculation of Escherichia coli.

OBJECTIVE: To determine whether concentrations of proinflammatory cytokines, acute-phase proteins, and cortisol differ at parturition among 3 categories of sows (noninoculated, clinically affected and nonaffected following intramammary inoculation with Escherichia coll). ANIMALS: 16 sows. PROCEDURE: Sows were allocated to inoculated (n = 12) or noninoculated (4) groups. Inoculated sows received intramammary administration of E coli (serotype O127) during the 24-hour period preceding parturition. Blood samples were collected from noninoculated and inoculated sows for 3 consecutive days within 3 to 11 days before farrowing and inoculation. Samples were also collected 0, 24, 48, 72, and 96 hours after farrowing and inoculation. Inoculated sows were further categorized as affected (4 sows) or nonaffected (8 sows) based on clinical signs of disease. Serum tumor necrosis factor (TNF)-alpha, plasma interleukin (IL)-6, and serum amyloid A (SAA) concentrations were measured by use of ELISA; serum haptoglobin concentration was assayed by use of a hemoglobin-binding method; and plasma cortisol concentration was determined by use of radioimmunoassay. RESULTS: Plasma or serum concentrations of TNF-alpha, IL-6, and SAA of both categories of inoculated sows were significantly increased by 24 hours after intramammary inoculation of E coli, compared with concentrations in noninoculated sows. Concentrations of serum TNF-alpha and plasma IL-6 were significantly higher in inoculated sows that developed clinical mastitis than in nonaffected inoculated sows. CONCLUSIONS AND CLINICAL RELEVANCE: Concentrations of TNF-alpha and IL-6 are promising markers for the identification of periparturient sows with subclinical coliform mastitis. Identification of such sows should help improve the health and survival of piglets.

Analysis of Variance↗

Haptoglobin and lipoperoxides in rabbit plasma under turpentine- and endotoxin-induced inflammation.

Inflammation was induced in rabbits by injection of turpentine or/and endotoxin. Haptoglobin (Hp) and lipoperoxide (as malondialdehyde - MDA) concentrations in rabbit plasma, were measured. In some experiments indomethacin was administered, as a specific control of anti-inflammatory action. In the course of the reagents-induced inflammation there existed positive correlation between changes in Hp and MDA levels. Indomethacin was found to eliminate this effect. Under the model system of experiments, Hp as presumed endogenous inhibitor of prostaglandin synthesis, even in concentrations in rabbits' blood 15-20 times higher than normal, did not exert any protective action against inflammation.

Animals↗

Haptoglobins in some Galliformes birds.

In several groups of galliform birds (chicken, turkey, pheasant and guinea fowl) the presence and function of plasma haptoglobin (Hp) have been studied. Paper, acetate and starch-gel electrophoresis were carried out and two benzidine stain regions were observed when haemoglobin (Hb) was added to normal plasma (Hb-Hp complex and methemalbumin) besides the free Hb when the binding capacity of these proteins were surpassed. The disappearance of the administered Hb-59Fe was exponential which is evidence of the existence of two different rates. Liver, bone marrow and kidney are the main organs related to the 59Fe uptake. These results on Hp in galliforms and the metabolism of the Hb are concordant with the data in the literature on mammals. This suggests the same common physiological role for Hp.

Animals↗

Differences in blood haptoglobin and length-mass relationships in river otters (Lutra canadensis) from oiled and nonoiled areas of Prince William Sound, Alaska.

Significant differences in levels of blood haptoglobin occurred between river otters (Lutra canadensis) inhabiting oiled (mean = 361 mg/100 ml, SD = 38, n = 6) and nonoiled (mean = 306 mg/100 ml, SD = 87, n = 8) areas of Prince William Sound, Alaska (USA) following the Exxon Valdez oil spill in 1989. Additionally, male river otters from oiled areas had significantly lower body mass (1.13 kg) than male otters from nonoiled areas. We propose oil-related causes for these differences.

Alaska↗

Evidence for recovery of body mass and haptoglobin values of river otters following the Exxon Valdez oil spill.

Levels of blood haptoglobin (Hp) and interleukin-6 immunoreactive protein (IL-6 ir) were significantly elevated in river otters (Lutra canadensis) inhabiting oiled areas of Prince William Sound, Alaska (USA) following the Exxon Valdez oil spill in 1989. By May and June 1992, however, such differences were not apparent. Mean body mass of otters, adjusted for sex, age-class, and total length with analysis of covariance, differed between oiled and non-oiled areas from 1990 to 1992, but were nearly identical by May and June 1992. We propose that river otters may be recovering from chronic effects that we observed in 1990 and 1991 following the 1989 Exxon Valdez oil spill, but further research is necessary to test this hypothesis.

Accidents↗

Plasma haptoglobin levels in threatened Alaskan pinniped populations.

We evaluated the plasma concentration of the acute phase protein haptoglobin (Hp) from Steller sea lions (Eumetopias jubatus) and harbor seals (Phoca vitulina) in regions of Alaska (USA) where the populations of these pinnipeds were declining and compared the values with concentrations of Hp from the same species in areas where the populations were stable. Samples were collected from 1992 through 1994 at sites in Southeast Alaska, Prince William Sound, the Gulf of Alaska, and the Aleutian Islands. Significantly higher levels of Hp were found in the samples from the areas of decline compared to those from stable populations. Based on these findings, we propose that one may be able to distinguish these compromised pinniped populations using Hp as a biomedical indicator.

Alaska↗

Serum haptoglobin concentrations in ringed seals (Pusa hispida) from Svalbard, Norway.

Haptoglobin (Hp) levels were measured in blood serum from 185 apparently healthy ringed seals (Pusa hispida) from Svalbard (age range, 1-30 yr) collected during the spring seasons of 2002 through 2004. The Hp concentration was 0.26 +/- 0.02 g/l (mean +/- SE; range, 0.0-1.5 g/l). Maturity status, body condition index (CI), interactions between CI and maturity status, and sex and maturity status all had significant influences on Hp levels. Mature males had significantly higher Hp concentrations compared with mature females (0.30 +/- 0.03 vs. 0.17 +/- 0.01 g/l, F(1,16) = 14.9, P<0.01). No differences were found between Hp levels in immature male and female seals (0.33 +/- 0.06 g/l). The Hp levels increased significantly in immature seals when the CI decreased. Despite the fact that mature males had a significantly lower CI than mature females, no direct correlation was found between Hp concentration and CI among adults. The elevated Hp values found in mature males might be related to injuries inflicted among males while fighting during the mating season or to high stress levels related to mating competition. The Hp concentrations of ringed seals measured in this study are useful baseline data for development of a diagnostic tool for future monitoring of the general health of this and other ringed seal populations.

Age Factors↗

Haptoglobin types in cancer patients in comparison with normal populations in the Eastern India.

The distribution of haptoglobin (Hp) phenotypes in patients with different types of cancer was compared with those in the normal population, with the aid of vertical disc polyacrylamide gel electrophoresis. The Hp1 gene frequency (0.0647) of the normal population exhibited only a slight difference from that of the cancer patients, as against previous records. The only appreciable difference was in the range of mobility of the Hp2 bands from the origin in individuals with Hp 2-1 and 2-2 phenotypes.

Electrophoresis, Polyacrylamide Gel↗

Distribution of hereditary variants of haptoglobin and transferrin in several human populations in Siberia.

Haptoglobins and transferrins have been studied in nganasans from Taymir peninsula, in chelkantsi and kumandintsi from Altai and in 500 Russian inhabitants of Novosibirsk. Frequencies of Hp2 and TfB0-1 alleles in nganasams have been found to be the highest in the region. Transferrin polymorphism in the sample from Novosibirsk population seems to be maintained at the expense of four common alleles (C;B2;B0-1; DChi), in nganasans -- tow alleles (C and B0-1). No polymorphism has been observed in chelkantsi and kumandintsi. No rare transferrin variant has been found in the samples studied except homozygous B0-1 B0-1 in a child from nganasan family.

Alleles↗

TNF-induced haptoglobin release from human neutrophils: pivotal role of the TNF p55 receptor.

Haptoglobin (Hp), TNF-alpha, and neutrophils are parts of a highly interactive ensemble participating in inflammatory processes. Hp is taken up by neutrophils, stored within a cytoplasmic granular compartment, and is secreted during phagocytosis by those cells. In the present study, the effects of TNF-alpha on the release of Hp from human neutrophils were investigated. Incubation of neutrophils with TNF-alpha induced the release of Hp from cells in a time- and concentration-dependent manner as revealed by Western blot analysis and immunofluorescence. The release of Hp induced by TNF-alpha was not due to nonspecific lysis of the cells. TNF-alpha is a highly pleiotropic cytokine that mediates its effects by binding to two distinct receptors (p55 and p75). Administration of TNF-alpha mutants binding specifically either to the p55 or to the p75 TNF receptors showed that there is a preference of TNF-alpha for the p55 receptor in the mediation of Hp release by neutrophils. A stimulated release of Hp was also induced by the chemotactic tripeptide fMLP. The TNF-alpha-induced release of Hp from neutrophils was inhibited by erbstatin, a tyrosine kinase inhibitor. These findings suggest that TNF-alpha may promptly increase the level of Hp at sites of infection or injury, leading to the modulation of the acute inflammatory response.

Antigens, CD↗

[The pathogenesis of abdominal aortic aneurysm and polymorphism of haptoglobin and inflammatory factor].

52 patients were operated on for abdominal aortic aneurysm and 38 for aortic occlusion disease. Haptoglobin (Hp) phenotypes were determined in all these patients. Hp and C-reactive protein (CRP) concentrations were determined in each phenotype. On the basis of the statistical analysis the highest percentage of elevated CRP concentrations was found in patients with abdominal aortic aneurysm and phenotype Hp 2-1.

Aged↗

The prevalence of type II diabetes mellitus is haptoglobin phenotype-independent.

Haptoglobin (Hp) phenotype distribution and the association between Hp polymorphism and type II diabetes mellitus was investigated in a Jordanian sample population consisting of 618 nondiabetics and 265 diabetics. In nondiabetics, Hp 2-2 was the most predominant type occurring at a frequency of 0.529 followed by Hp 2-1 occurring at a frequency of 0.387. In diabetics, the Hp 2-2 frequency was 0.540 while that of Hp 2-1 was 0.381. No statistically significant variation was detected in Hp type distribution between the two groups. The Hp2 allele occurred at a frequency of 0.722 in nondiabetics and 0.730 in diabetics. In both groups, the Hp type distribution was in agreement with the Hardy-Weinberg equilibrium calculations. These results suggest that type II diabetes mellitus is Hp phenotype-independent.

Adult↗