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PubMed1996

Haptoglobin response to clinical respiratory tract disease in feedlot cattle.

OBJECTIVE: To quantify haptoglobin response to respiratory tract disease in feedlot cattle, and to investigate its ability to predict disease outcome and response to antibiotic treatment. DESIGN: Randomized clinical trial. ANIMALS: 60 feedlot calves with clinical respiratory tract disease. PROCEDURE: Calves were randomly assigned to receive a standard antibiotic treatment regimen (TRT), or to observation pens without antibiotic treatment. Serum haptoglobin concentration was measured at initial and final examinations. Calves were examined for presence of gross pulmonary lesions at slaughter. RESULTS: Mean +/- SD serum haptoglobin concentration at initial examination was 67 +/- 108 mg/dl, with range of 0 to 508 mg/dl. Haptoglobin concentration at initial examination was similar for the TRT group and the group that did not receive antibiotic treatment, but at final examination, TRT-group calves had lower (P < 0.01) mean values. Calves receiving antibiotic treatment had haptoglobin concentration at or near zero at final examination. Calves not receiving antibiotic treatment had only slightly lower mean haptoglobin concentration at final examination, compared with initial examination. Within treatment groups, haptoglobin concentration was similar for cases with different outcomes. Calves with gross pulmonary lesions at slaughter had numerically higher, although statistically similar, haptoglobin concentrations at initial examination, compared with calves without lesions. CONCLUSIONS: Feedlot cattle with clinical respiratory tract disease have a large and variable haptoglobin response. Antibiotic treatment resulted in lower serum haptoglobin values, although low values were not required for full clinical recovery. CLINICAL RELEVANCE: Serum haptoglobin concentration may be an indicator of response to antibiotic therapy, although it appears to be unrelated to case severity or need for treatment.

Animals↗
PubMed2006

Validation of a commercially available human immunoturbidimetric assay for haptoglobin determination in canine serum samples.

Haptoglobin is a positive acute-phase protein with a valuable role as a marker of inflammation in both human and veterinary medicine. The aim of this study was to validate a commercially available immunoturbidimetric method designed for human haptoglobin determination (Izasa SA, Barcelona, Spain) for its use in canine samples. Cross-reactivity between anti-human haptoglobin antiserum and canine haptoglobin was found when agarose gel immunodiffusion and ELISA tests were performed. The use of canine pooled serum with haptoglobin concentration of 6.3 g/L as standard provided higher analytical range than commercially available standards. Intra-assay and inter-assay coefficients of variation were 2.49% and 4.60%, respectively. A linear regression model between immunoturbidimetric results and a previously validated spectrophotometric method (Tridelta Development Limited, Ireland) yielded a slope at 95% confidence interval of 0.94 (0.86, 1.02) and y-intercept at 95% confidence interval of 0.11 (-0.59, 0.82). No significant differences were produced by anticoagulants, lipaemia and bilirubinaemia, although haemolysis significantly decreased haptoglobin. A significant increase of haptoglobin concentration was detected in inflammatory conditions such as pyometra and leishmaniasis, in neoplastic conditions, and after glucocorticoid administration. Canine serum haptoglobin concentration can be reliably measured using the commercially available Izasa immunoturbidimetric method developed for human haptoglobin determination. This method is precise and accurate, provides a wider analytical range than previous reported methods, and can be easily automated and used for routine haptoglobin determination in canine samples.

Animals↗
PubMed2002

Haptoglobin phenotype and the risk of restenosis after coronary artery stent implantation.

We recently demonstrated that an allelic polymorphism in the haptoglobin gene is a major determinant of susceptibility to a number of vascular disorders. We set out to determine if haptoglobin phenotype was predictive of the development of restenosis in a consecutive series of patients, all of whom underwent stent implantation followed by repeat angiography with quantitative coronary angiography analysis 6 months later. This study included 214 consecutive patients undergoing stent implantation for de novo lesions between 1998 and 1999 in Aalst, Belgium. All underwent follow-up quantitative coronary angiography analysis 6 months after the procedure. The haptoglobin phenotype was determined by electrophoresis. No significant differences were found between patients segregated by phenotype with respect to clinical, procedural, and angiographic factors previously suggested to influence the development of restenosis. None of the diabetic patients homozygous for the haptoglobin 1 allele developed restenosis compared with a >50% restenosis rate for diabetic patients with at least 1 haptoglobin 2 allele (p <0.02). In all patients (diabetic and nondiabetic), we observed a trend toward a lower incidence of restenosis in patients homozygous for the 1 allele (21% vs 33%, p <0.09). Moreover, we found a graded risk relation to the number of haptoglobin 2 alleles. The risk of developing restenosis was greater in subjects with 2 haptoglobin 2 alleles (36%) than in those with 1 haptoglobin 2 allele (31%) or no haptoglobin 2 alleles (21%). Thus, knowledge of the haptoglobin phenotype may be useful in assessing and utilizing new therapies that attempt to reduce restenosis, and may have important implications for the risk stratification algorithm used in managing diabetic patients with coronary artery disease.

Aged↗
PubMedDate not supplied

Detection of serum haptoglobin by enzyme-linked immunosorbent assay in cows with fatty liver.

Haptoglobin cannot be detected in the serum of healthy cattle by the haemoglobin-binding assay or single radial immunodiffusion. The present study was designed to examine whether an enzyme-linked immunosorbent assay could be applied to measure serum haptoglobin concentrations in healthy cows and in cows with fatty liver. When either purified cow haptoglobin or haptoglobin-positive serum were used as the antigen in the assay, the standard curves obtained were distinctly different, and haptoglobin in serum was detected more sensitively than the purified protein. The addition of bovine serum albumin to purified haptoglobin shifted the curve towards that obtained with haptoglobin-positive serum, suggesting that an interaction with serum albumin was partly responsible for the different standard curves. By use of the standard curve for haptoglobin in serum, the mean (SEM) concentration of haptoglobin in samples from four cows with fatty liver was 466 (147) micrograms ml-1, but the sera from four apparently healthy cows contained less than 0.01 microgram ml-1 haptoglobin.

Animals↗
PubMed1998

Cross reactivities among some mammalian haptoglobins studied by a monoclonal antibody.

Mouse monoclonal antibody antihuman-Hp, product of clone 2.36.71.41 was found to recognize, however, with different affinities, the immunological determinant on haptoglobin of some mammals (goat, sheep, cow, horse, rabbit). The following differences in immunological cross reactivities were noticed: (i) haptoglobins present in sera of goat, sheep and cow (Artiodactyla, Bovidae) react in enzyme-linked immunosorbent assay (ELISA) and form precipitates in agarose gel; (ii) horse (Perissodactyla) and rabbit (Lagomorpha) haptoglobins react in ELISA, but they do not form precipitates; and (iii) haptoglobins of dog, fox, cat (Carnivora) and pig (Artiodactyla, Suidae) are not recognized by the tested monoclonal antibody either in ELISA or in agarose gel. This study suggests that monoclonal antibody, clone 2.36.71.41, recognizes the structure on haptoglobin around the disulphide bond linking two alpha chains. Antigenic structure of Bovidae haptoglobins is rather similar to human haptoglobin 2-2 (circular polymers) than to 2-1 type (linear polymers). Monoclonal antibody 2.36.71.41 could be used for classification of mammalian haptoglobins by epitope structure. It can distinguish polymeric haptoglobins similar to human type 2-2 from other mammalian haptoglobins.

Animals↗
PubMed2004

Haptoglobin phenotype correlates with development of cardiac transplant vasculopathy.

OBJECTIVES: The purpose of this study was to investigate the association between haptoglobin phenotypic variation and development of cardiac transplant vasculopathy. BACKGROUND: The development of coronary vasculopathy determines long-term survival after cardiac transplantation. Serum haptoglobin levels are associated with non-transplant atherosclerosis. In addition to free hemoglobin binding, haptoglobin influences free radical formation, prostaglandin synthesis and angiogenesis. Three phenotypes of haptoglobin exist in humans, which have both quantitative and qualitative differences. METHODS: Coronary disease was diagnosed at post-transplant routine surveillance angiography. Hemoglobin (10%) was added to recipient plasma to form a haptoglobin-hemoglobin complex. Sample aliquots were applied to acid hemoglobin plates and electrophoretically separated. Phenotypes were recognized by comparing the electrophoretic pattern with that of established standards. Haptoglobin concentrations were measured using an immunoturbidimetric technique with polyethylene glycol (PEG)-enhanced precipitation. RESULTS: Ninety-three patients were independently studied. Phenotype 1-1 was found in 20.4%, 2-1 in 41.9% and 2-2 in 37.6%. Haptoglobin levels were highest in 1-1 recipients (2.1 +/- 0.58 g/liter) compared with 1.78 +/- 0.88 g/liter and 1.3 +/- 0.81 g/liter in 2-1 and 2-2 individuals, respectively (p = 0.001). Haptoglobin phenotype was significantly related to the development of vasculopathy; recipients with a 2-1 phenotype were more likely to develop angiographic disease (p = 0.0084). No differences were found among the 3 groups according to univariate analysis. Multivariate analysis identified 3 risk factors for vasculopathy development: age of donor (hazard ratio 1.056 [95% confidence interval 1.02 to 1.094], p = 0.0023); pre-transplant recipient body mass index (hazard ratio 1.116 [95% confidence interval 1.015 to 1.23], p = 0.024), and haptoglobin phenotype (hazard ratio 2.725 [95% confidence interval 1.031 to 7.19], p = 0.012). CONCLUSIONS: Haptoglobin, through phenotype-dependent mechanisms, correlates with the development of coronary vasculopathy. This finding furthers our understanding of the disease, opens up new areas of research, and may lead to novel therapies.

Adult↗
PubMed2003

The acute phase protein haptoglobin is locally expressed in arthritic and oncological tissues.

Haptoglobin is an acute phase protein known to be highly expressed in the liver. Recently, we showed increased local arterial haptoglobin expression after flow-induced arterial remodelling and found that haptoglobin is involved in cell migration and arterial restructuring probably through accumulation of a temporary gelatin matrix. Since cell migration and matrix turnover are important features in the pathology of arthritis and cancer, we hypothesized that haptoglobin is also locally expressed in arthritic and oncological tissues. In this study, we investigated local haptoglobin expression in arthritic rats (n = 12) using semi-quantitative PCR and Western blotting, and we studied haptoglobin mRNA localization in human kidney tumours (n = 3) using in situ hybridization. The arthritic rats demonstrated an increase of haptoglobin mRNA (2.5-fold, P < 0.001) and protein (2.6-fold, P < 0.001) in the arthritic Achilles tendon. Haptoglobin protein was also increased in the arthritic ankle (2.6-fold, P < 0.001) but not in the non-arthritic knee. In human kidney tumours, tumour and stromal cells produced haptoglobin mRNA. This study shows that the liver protein haptoglobin is, in addition to the artery, also expressed in arthritic and oncological tissues that are recognized for enhanced cell migration and matrix turnover.

Animals↗
PubMed2003

Haptoglobin polymorphism is a risk factor for cardiovascular disease in patients with obstructive sleep apnea syndrome.

STUDY OBJECTIVES: Obstructive sleep apnea syndrome is associated with a marked increase in the risk for cardiovascular disease. Increased oxidative stress and leukocyte adhesiveness have been implicated as fundamental pathophysiologic mechanisms underlying the increased susceptibility in these patients. Haptoglobin is an antioxidant and immunomodulatory protein encoded by 2 alleles with profoundly different biophysical and biochemical properties. We therefore sought to determine if the haptoglobin phenotype was a determinant of cardiovascular disease in patients with obstructive sleep apnea syndrome. DESIGN: Haptoglobin phenotype was determined by gel electrophoresis in 465 patients with and 757 individuals without obstructive sleep apnea syndrome. SETTING: Eight-bed Technion Sleep Medicine Center in Haifa, serving the northern part of Israel. PARTICIPANTS: Patients referred for sleep recordings because of suspected breathing disorders in sleep and healthy industry workers. MEASUREMENTS AND RESULTS: Patients with obstructive sleep apnea syndrome and cardiovascular disease had a significantly different distribution of the 3 haptoglobin phenotypes as compared to patients with obstructive sleep apnea syndrome but without cardiovascular disease. No difference in the haptoglobin phenotype frequency was found between controls with and without cardiovascular disease. Log linear analysis revealed a significant interaction effect of haptoglobin phenotype and the presence of sleep apnea on the presence of cardiovascular disease. Logistic regression analysis revealed that the risk of cardiovascular disease in sleep apnea patients younger than 55 years with haptoglobin 2-2 was 2.32-fold higher than in their counterparts with haptoglobin 2-1. CONCLUSIONS: These results suggest that haptoglobin phenotype is an important risk factor in determining susceptibility to cardiovascular disease in obstructive sleep apnea syndrome, which may be mediated by the decreased antioxidant and antiinflammatory actions of the haptoglobin 2 allelic protein product.

Alleles↗
PubMed2001

Hemolysis in stored red blood cell concentrates: modulation by haptoglobin or ulinastatin, a protease inhibitor.

OBJECTIVE: Polymorphonuclear leukocyte elastase may injure various tissues. The release of polymorphonuclear leukocyte elastase induced by various stimuli was reported to be inhibited by a protease inhibitor, ulinastatin. In stored blood preparations, polymorphonuclear leukocyte elastase increases depending on the storage days as hemolysis increases. We hypothesized that polymorphonuclear leukocyte elastase might be one of the factors inducing hemolysis in stored blood. Haptoglobin binds to free hemoglobin to reduce hemolysis. The purpose of the study was to investigate the effects of ulinastatin on hemolysis in blood preparations in comparison with haptoglobin. DESIGN: In vitro study. SETTING: Laboratory in a university hospital. SUBJECTS: Nine 2-day-old packs of red blood cell concentrates (CRC) in 400 mL each of mannitol, adenine, glucose, phosphate, and citrate (MAP) (MAP-CRC) from the Japan Red Cross Society. INTERVENTIONS: Each MAP-CRC was divided into three different packs of equal amount and was treated with 10 mL of saline (control group), 200 units of haptoglobin, or 50,000 units of ulinastatin. They were stored at 4 degrees C. MEASUREMENTS AND MAIN RESULTS: Supernatant concentrations of total and free hemoglobin, total haptoglobin, polymorphonuclear leukocyte elastase, and potassium were measured for 25 days. Free haptoglobin concentration was calculated. Total and free hemoglobin concentrations increased significantly depending on the storage days in the control group, whereas haptoglobin and ulinastatin groups showed no increase. Total and free haptoglobin concentrations were significantly higher in the haptoglobin group than in the other two groups. Free haptoglobin concentrations were 0 after 5 days of storage in the control and ulinastatin groups. Polymorphonuclear leukocyte elastase concentrations increased with the increase in storage days without any differences among the three groups. Potassium concentration increased according to the storage and showed the highest value in the control group. CONCLUSIONS: Adding haptoglobin or ulinastatin to MAP-CRC was useful to suppress hemolysis during storage of the preparation. The polymorphonuclear leukocyte elastase might not be involved in the mechanisms of hemolysis in MAP-CRC stored for 25 days.

Blood Banks↗
PubMed2001

Structure-function analysis of the antioxidant properties of haptoglobin.

Haptoglobin serves as an antioxidant by virtue of its ability to prevent hemoglobin-driven oxidative tissue damage. It was recently demonstrated that an allelic polymorphism in the haptoglobin gene is predictive of the risk for numerous microvascular and macrovascular diabetic complications. Because these complications are attributed in large part to an increase in oxidative stress, a study was conducted to determine whether the different protein products of the 2 haptoglobin alleles differed in the antioxidant protection they provided. A statistically significant difference was found in the antioxidant capacity of purified haptoglobin protein produced from the 2 different alleles, consistent with the hypothesis that differences in genetically determined antioxidant status may explain differential susceptibility to diabetic vascular complications. These differences may be amplified in the vessel wall because of differences in the sieving capacity of the haptoglobin types. Therefore, an attempt was made to identify the minimal haptoglobin sequences necessary to inhibit oxidation by hemoglobin in vitro, and 2 independent haptoglobin peptides that function in this fashion as efficiently as native haptoglobin were identified. Identification of the biochemical basis for differences among haptoglobin types may lead to the rational development of new pharmacologic agents, such as the mini-haptoglobin described here, to avert the development of diabetic vascular complications.

Alleles↗
PubMed2003

Haptoglobin release by human adipose tissue in primary culture.

Haptoglobin is a putative adiposity marker because its concentration in blood is increased in obese humans. The present studies examined haptoglobin release by explants of adipose tissue in primary culture. Haptoglobin was released by explants of human visceral and subcutaneous adipose tissue at a nearly linear rate over 48 h. Explants of visceral adipose tissue released more haptoglobin than did explants of subcutaneous adipose tissue. The release of haptoglobin was quite variable, but there was a close correlation between haptoglobin release by visceral adipose tissue and that by explants of subcutaneous tissue from the same individual. Dexamethasone and niflumic acid, a cyclooxygenase-2 inhibitor, both inhibited haptoglobin release. There was release of haptoglobin by both isolated adipocytes and the adipose tissue matrix remaining after collagenase digestion of human adipose tissue. However, the amount of haptoglobin released by human adipose tissue explants in primary culture was quite low in relationship to the circulating level of haptoglobin.

Adipose Tissue↗
PubMed2002

Genotyping of the common haptoglobin Hp 1/2 polymorphism based on PCR.

BACKGROUND: A genetically defined molecular heterogeneity of haptoglobin, characterized by the major phenotypic forms Hp 1-1, Hp 2-1, and Hp 2-2, has been associated with distinct clinical manifestations. To enable the use of DNA samples for the study of this polymorphism, we established a haptoglobin genotyping method based on PCR. METHODS: Taking advantage of the selectivity of PCR, we amplified DNA segments specifically representing haptoglobin alleles Hp 1 and Hp 2 from genomic DNA. The products were analyzed by agarose gel electrophoresis. Haptoglobin phenotyping of plasma samples was performed by polyacrylamide gel electrophoresis and peroxidase staining. RESULTS: Exploiting the known size difference between Hp 1 and Hp 2, we amplified allele-specific DNA molecules with one pair of oligonucleotide primers. As an alternative, we used separate primer pairs to generate amplification products indicative of alleles Hp 1 and Hp 2. Because of the primer design, genotype determination was not compromised by sequence variations specifying haptoglobin allele subtypes S and F. For the same reason, the sequence similarity between the haptoglobin gene and the haptoglobin-related gene did not interfere with the accuracy of genotyping. Analysis with restriction enzymes demonstrated the authenticity of the allele-specific DNA products. Haptoglobin DNA genotyping and protein phenotyping, performed in parallel, yielded fully corresponding results. In a group of 249 individuals, the haptoglobin genotype distribution was as follows: 14.5% Hp 1-1, 48.2% Hp 2-1, and 37.3% Hp 2-2. CONCLUSION: The new method can be used for genotyping of a common haptoglobin polymorphism.

DNA↗
PubMed2005

The impact of controlled release capsules of monensin on postcalving haptoglobin concentrations in dairy cattle.

This study was designed to assess the impact of a controlled release capsule (CRC) of monensin, administered prior to calving, on postcalving haptoglobin levels. The role of disease on haptoglobin levels was also studied. The study population consisted of 1010 cows from 25 Holstein dairy herds near Guelph, Ontario. Monensin CRC or placebo capsules were randomly assigned within each herd 3 wk prior to the expected calving date. Serum from week 1 and week 6 postcalving was submitted for quantification of haptoglobin concentrations. Haptoglobin results were analyzed for associations with treatment, health data, and individual cow factors up to 95 d in milk. Haptoglobin concentrations were higher in week 1 than week 6 (P < 0.05). In univariate analysis, several diseases were significantly associated with haptoglobin concentrations. However, occurrence of disease appeared to be a confounding factor in the data interpretation. Thus, the analysis was stratified by the presence or absence of disease. There appeared to be associations between factors other than clinical disease contributing to increased haptoglobin levels in both clinically healthy and unhealthy cattle. Haptoglobin served as a good indicator of inflammatory disease. Monensin CRC treatment was associated with increased haptoglobin concentrations in clinically unhealthy cattle, perhaps reflecting a better ability to respond to disease challenge. The lower haptoglobin concentrations in monensin CRC treated cattle that were clinically normal may be a reflection of reduced subclinical disease.

Animals↗
PubMed2006

Fucosylated haptoglobin is a novel marker for pancreatic cancer: a detailed analysis of the oligosaccharide structure and a possible mechanism for fucosylation.

Changes in oligosaccharide structures have been reported in certain types of malignant transformations and, thus, could be used for tumor markers in certain types of cancer. In the case of pancreatic cancer cell lines, a variety of fucosylated proteins are secreted into their conditioned media. To identify fucosylated proteins in the serum of patients with pancreatic cancer, we performed western blot analyses using Aleuria Aurantica Lectin (AAL), which is specific for fucosylated structures. An approximately 40 kD protein was found to be highly fucosylated in pancreatic cancer and an N-terminal analysis revealed that it was the beta chain of haptoglobin. While the appearance of fucosylated haptoglobin has been reported in other diseases such as hepatocellular carcinoma, liver cirrhosis, gastric cancer and colon cancer, the incidence was significantly higher in the case of pancreatic cancer. Fucosylated haptoglobin was observed more frequently at the advanced stage of pancreatic cancer and disappeared after an operation. A mass spectrometry analysis of haptoglobin purified from the serum of patients with pancreatic cancer and the medium from a pancreatic cancer cell line, PSN-1, showed that the alpha 1-3/alpha 1-4/alpha 1-6 fucosylation of haptoglobin was increased in pancreatic cancer. When a hepatoma cell line, Hep3B, was cultured with the conditioned media from pancreatic cancer cells, haptoglobin secretion was dramatically increased. These findings suggest that fucosylated haptoglobin could serve as a novel marker for pancreatic cancer. Two possibilities were considered in terms of the fucosylation of haptoglobin. One is that pancreatic cancer cells, themselves, produce fucosylated haptoglobin; the other is that pancreatic cancer produces a factor, which induces the production of fucosylated haptoglobin in the liver.

Biomarkers, Tumor↗
PubMed1964

IMMUNOLOGICAL AND BIOCHEMICAL STUDIES ON SERUM HAPTOGLOBIN.

Antibody to purified type 1-1 human serum haptoglobin was obtained in rabbits. Using this antiserum it was demonstrated that the antigenic determinants of the haptoglobin molecule reside in both alpha- and beta-chains. No immunological difference between the normal alpha(1F)- and alpha(1S)-chains of haptoglobin could be detected. A number of healthy individuals whose haptoglobin pattern appeared normal by starch gel electrophoresis were shown to possess a haptoglobin which could be distinguished immunologically from the common haptoglobin types. These immunological atypical haptoglobins have been observed in individuals of types 1-1, 2-1, and 2-2. Combined immunological and chemical studies of purified haptoglobin have enabled the construction of a tentative model for the structure of human type 1-1 haptoglobin.

Animals↗
PubMed1990

Specific binding of haptoglobin to human neutrophils and its functional consequences.

Haptoglobin, an acute phase reactant protein, has been shown to modulate various facets of immune responses. In this paper we examined the effect of haptoglobin on human neutrophils at the molecular level. First, we found that native haptoglobin binds at two distinct sites on neutrophils. We then examined the effects of this binding at normal and pathophysiological concentrations of haptoglobin found in human serum. Of the various functional parameters assessed, neutrophil respiratory burst activity, as assessed by superoxide (O2-) production, was inhibited by native haptoglobin when the cells were stimulated with formylmethionyl-leucylphenylalanine (FMLP), arachidonic acid (AA), and opsonized zymosan. The rise in intracellular calcium induced by FMLP stimulation was also inhibited by native haptoglobin. Since the generation of O2- was unaffected by native haptoglobin in phorbol myristate acetate (PMA)-stimulated neutrophils, the likely site of haptoglobin inhibition on neutrophil function is at a point of receptor-ligand interaction in the activation cascade. The role of haptoglobin as a modifier of the immune response has here been extended to altered neutrophil function stimulated by diverse agonists.

Calcium↗
PubMed2001

Haptoglobin phenotype and diabetic nephropathy.

AIMS/HYPOTHESIS: To determine if the haptoglobin 2 allele is associated with an increased risk for the development of diabetic nephropathy. METHODS: This study included 110 consecutive normotensive subjects with Type I (insulin-dependent) diabetes mellitus and Type II (non-insulin-dependent) diabetes mellitus seen in two outpatient clinics in Israel. Diabetes duration was greater than 10 years for Type I diabetes and more than 5 years for Type II diabetic subjects. Microalbuminuria was defined as urinary protein excretion of 30 to 300 mg/24 h, and macroalbuminuria was defined as urinary protein excretion of greater than 300 mg/24 h. Serum was taken from subjects for haptoglobin typing by gel electrophoresis. RESULTS: Of the participating subjects 54 had Type I and 56 had Type II diabetes. None (0/18) of the subjects homozygous for the haptoglobin 1 allele (1-1) showed any sign of diabetic nephropathy, as compared with 34 % (19/55) of subjects homozygous for the haptoglobin 2 allele (2-2) and 27 % (10/37) of heterozygous subjects (2-1) (p < 0.04). Of the subjects 29 showed macroalbuminuria. The risk of developing macroalbuminuria was found to be greater in subjects with two haptoglobin 2 alleles (22 %) (12/55) as compared with one haptoglobin 2 allele (8 %) (3/37) or no haptoglobin 2 alleles (0%) (0/18) (p < 0.03). CONCLUSION/INTERPRETATION: By showing a graded risk relation to the number of haptoglobin 2 alleles in Type I and Type II diabetic subjects, these studies further support our hypothesis that the haptoglobin phenotype is a major susceptibility gene for the development of diabetic nephropathy.

Albuminuria↗
PubMed2002

Haptoglobin phenotype is an independent risk factor for cardiovascular disease in individuals with diabetes: The Strong Heart Study.

OBJECTIVES: The goal of this study was to determine if the haptoglobin phenotype was predictive of cardiovascular disease (CVD) in diabetic mellitus (DM). BACKGROUND: Cardiovascular disease is the most frequent, severe, and costly complication of type 2 DM. There are clear geographic and ethnic differences in the risk of CVD among diabetic patients that cannot be fully explained by differences in conventional CVD risk factors. We have demonstrated that a functional allelic polymorphism in the haptoglobin gene acts as a major determinant of susceptibility for the development of diabetic microvascular complications. METHODS: We sought to determine if this paradigm concerning the haptoglobin gene could be extended to CVD in DM. We tested this hypothesis in a case-control sample from the Strong Heart study, a population-based longitudinal study of CVD in American Indians. Haptoglobin phenotype was determined by polyacrylamide gel electrophoresis in 206 CVD cases and 206 matched controls age 45 to 74 years. Median follow-up was six years. RESULTS: In multivariate analyses controlling for conventional CVD risk factors, haptoglobin phenotype was a highly statistically significant, independent predictor of CVD in DM. The odds ratio of having CVD in DM with the haptoglobin 2-2 phenotype was 5.0 times greater than in DM with the haptoglobin 1-1 phenotype (p = 0.002). An intermediate risk of CVD was associated with the haptoglobin 2-1 phenotype. CONCLUSIONS: This study suggests that determination of haptoglobin phenotype may contribute to the algorithm used in CVD risk stratification, and in evaluation of new therapies to prevent CVD in the diabetic patient.

Aged↗