HP Phenotype Research Articles

Haptoglobin polymorphism modulates cardiometabolic impacts of four consecutive weeks, dawn to sunset Ramadan intermittent fasting among subjects with overweight/obesity

AimsHaptoglobin (Hp) is a multifaceted marker of inflammation, and mediates the interplay between obesity, inflammation, and cardiometabolic dysfunction. However, the role of the Hp phenotype in modulating intermittent fasting (IF)-induced cardiometabolic changes remains to be elucidated. MethodsHp phenotype was determined for the study subjects. Cardiometabolic markers were assessed before and at the end of four consecutive weeks, dawn to sunset IF. ResultsA total of 114 subjects (75 males and 39 females, 38.7 ± 11.7 years, body mass index (BMI) of 30.41 ± 5.09 kg/m2) were recruited. Hp2-2 (n = 55, 48.2 %) and Hp2-1 (n = 53, 46.5 %) were the predominant phenotypes. Significant reductions were observed in serum Hp, IL-6, TNF-α, triglycerides (TG), total cholesterol (TC), LDL, BMI, and fat mass (FM), while a significant elevation was observed in serum CD163, HDL, and IL-10 at the end of the IF month for the whole population. Based on the Hp polymorphism, significant decreases in Hp, BMI, FM, TG, LDL, and TNF-α, with significant increases in HDL and CD163 levels were observed among subjects with Hp2-2 and Hp2-1 phenotypes. A more pronounced reduction in FM was reported in subjects with Hp2-2 in comparison with Hp2-1. ConclusionHp gene polymorphism modulates IF-induced changes in cardiometabolic markers.Clinical Trial Registration number: ISRCTN18205186; https://trialsearch.who.int/?TrialID=ISRCTN18205186.

Progress on haptoglobin and metabolic diseases.

Haptoglobin (Hp) is an acidic glycoprotein, existing in the serum and other body fluids of human beings and a variety of mammals. Hp is produced in the liver, white adipose tissue, and the kidney. The genetic polymorphisms and different phenotypes of Hp have different biological functions. Hp has antibacterial, antioxidant, and angiogenic effects and is associated with multiple diseases including simple obesity, vascular complications of diabetes mellitus, nonalcoholic fatty liver disease, hypertension, blood diseases, autoimmune diseases, and malignant tumors. Hp also participates in many life activities, indicating the importance of Hp in further studies. Previously, we found that the expression of serum Hp changed after treatment of simple obesity patients in clinical trials. However, the specific mechanism of Hp in patients with simple obesity is still unclear. The purpose of this article is to introduce recent research progress on Hp, emphasizing the relationship between Hp and the development of metabolic disease, which will improve the understanding of the functions of Hp underlying metabolic diseases and discuss future research directions.

Haptoglobin as a biomarker

Haptoglobin (Hp) is a blood plasma glycoprotein that binds free hemoglobin (Hb) and plays a critical role in tissue protection and the prevention of oxidative damage. In addition, it has a number of regulatory functions. Haptoglobin is an acute phase protein, its concentration in plasma changes in pathology, and the test for its concentration is part of normal clinical practice. Haptoglobin is a conservative protein synthesized mainly in the liver and lungs and is the subject of research as a potential biomarker of many diseases, including various forms of malignant neoplasms. Haptoglobin has several unique biophysical characteristics. Only in humans, the Hp gene is polymorphic, has three structural alleles that control the synthesis of three major phenotypes of Hp, homozygous Hp1-1 and Hp2-2, and heterozygous Hp2-1, determined by a combination of allelic variants that are inherited. Numerous studies indicate that the phenotype of haptoglobin can be used to judge the individual's predisposition to various diseases. In addition, Hp undergoes various post-translational modifications (PTMs). These are structural transformations (removal of the signal peptide, cutting of the Pre-Hp precursor molecule into two subunits, α and β, limited proteolysis of α-chains, formation of disulfide bonds, multimerization), as well as chemical modifications of α-chains and glycosylation of the β-chain. Glycosylation of the β-chain of haptoglobin at four Asn sites is the most important variable PTM that regulates the structure and function of the glycoprotein. The study of modified oligosaccharides of the Hp β-chain has become the main direction in the study of pathological processes, including malignant neoplasms. Many studies are focused on the identification of PTM and changes in the level of the α2-chain of this protein in pathology. These characteristics of Hp indicate the possibility of the existence of this protein as different proteoforms, probably with different functions. This review is devoted to the description of the structural and functional diversity of Hp and its potential use as a biomarker of various pathologies.

Haptoglobin Phenotypes Are Associated with the Postload Glucose and Insulin Levels in Pediatric Obesity.

Purpose Haptoglobin (Hp) is a protein involved in the acute-phase reaction of inflammation. Humans have three major phenotypes (Hp1-1, Hp1-2, and Hp2-2). Several studies have shown altered Hp regulation in adults with obesity and metabolic alterations. The Hp2-2 phenotype is associated with a high cardiovascular risk. Our aim was to investigate if Hp levels and the Hp2-2 phenotype are associated with glucose metabolism in pediatric obesity. Methods We retrospectively studied 192 participants (92 males and 100 females), aged 4–18 years. Clinical and biochemical data were collected. The Hp phenotype (Hp1-1, Hp1-2, and Hp2-2) was identified through Western immunoblot. Results Subjects carrying Hp1-1, Hp1-2, and Hp2-2 phenotypes were 13.6, 50.8, and 35.6%, respectively. Hp serum, fasting glucose, and insulin levels, as well as HOMA-IR, were similar among groups. Postload glucose and insulin levels (as insulin AUC) were progressively higher from the Hp1-1 to Hp2-2 phenotype. Conclusion To our knowledge, this is the first study on Hp phenotypes conducted in a pediatric population with obesity. We showed that the presence of Hp2 allele is associated with a worse response of glucose load in terms of both glucose and insulin levels. Thus, the Hp2-2 phenotype could predispose in pediatrics, at the same degree of obesity, to a worse glycemic and insulinemic compensation.

Cord Blood Haptoglobin, Cerebral Palsy and Death in Infants of Women at Risk for Preterm Birth: A Secondary Analysis of a Randomised Controlled Trial

BackgroundAntenatal exposure to intra-uterine inflammation results in precocious Haptoglobin (Hp) expression (switch-on status). We investigated the relationships between foetal Hp expression at birth with newborn and childhood outcomes. MethodsWe evaluated cord blood samples from 921 newborns of women at imminent risk for preterm delivery randomised to either placebo (n = 471, birth gestational age (GA) median [min-max]: 31 [24–41] weeks) or magnesium sulphate (n = 450, GA 31 [24–42] weeks]). Primary outcome was infant death by 1 year and/or cerebral palsy (CP) ≥2 years of corrected age. Adjusted odd ratios (aOR) for neonatal and childhood outcomes were calculated controlling for GA, birth weight, sex, and magnesium exposure. FindingsPrimary outcome occurred in 2.8% of offspring. Newborns were classified in three pre-defined categorisation groups by cord blood Hp switch status and IL-6 levels: inflammation-nonexposed (Category 1, n = 432, 47%), inflammation-exposed haptoglobinemic (Category 2, n = 449, 49%), and inflammation-exposed anhaptoglobinemic or hypohaptoglobinemic (Category 3, n = 40, 4%). Newborns, found anhaptoglobinemic or hypohaptoglobinemic (Category 3) had increased OR for intraventricular haemorrhage (IVH) and/or death (aOR: 7.0; 95% CI: 1.4–34.6, p = 0.02) and for CP and/or death (aOR: 6.27; 95% CI: 1.7–23.5, p = 0.006) compared with Category 2. Foetal ability to respond to inflammation by haptoglobinemia resulted in aOR similar to inflammation-nonexposed newborns. Hp1-2 or Hp2-2 phenotypes protected against retinopathy of prematurity (aOR = 0.66; 95% CI 0.48–0.91, p = 0.01). InterpretationFoetal ability to switch-on Hp expression in response to inflammation was associated with reduction of IVH and/or death, and CP and/or death. Foetuses unable to mount such a response had an increased risk of adverse outcomes.Trial Registration: clinicaltrials.gov Identifier: NCT00014989

223. CD163-mediated hemoglobin-scavenging system, haptoglobin phenotype and preeclampsia risk

Introduction Preeclampsia (PE) is a multisystemic disorder which complex pathophysiology involves both oxidative stress and endothelial dysfunction as key factors. The CD163-mediated haptoglobin (HP) hemoglobin-scavenging system has been proposed as an important pathway for diverse disease states due to its anti-inflammatory and pro-angiogenic effects. The human HP locus is polymorphic, yielding three distinct phenotypes characterized by different antioxidant and pro-angiogenic properties. Objective We aimed to determine whether HP phenotype was associated with PE risk and to assess the relationship between HP phenotype and first-trimester concentrations of HP, soluble form of the hemoglobin-scavenger receptor CD163 (sCD163), placental growth-factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1). Methods Case-control study of 452 pregnant women selected from a prospective cohort of singleton pregnancies that underwent first-trimester aneuploidy screening in a routine care low-risk setting. The study sample included 204 women who subsequently developed PE and 248 women with normal pregnancies who were matched for gestational age. HP phenotypes were determined by polyacrylamide gel electrophoresis (PAGE). First-trimester serum PlGF, sFlt-1 and HP concentrations were determined by automated electrochemiluminescence/immunoturbidimetric methods (Roche Diagnostics), while sCD163 levels were determined by enzyme-linked immunosorbent assay (R&D Systems). Results Although HP phenotype alone did not affect overall PE risk, we found significantly higher HP concentrations between preeclamptic and normal women with HP2-1 (122.0/107.1 mg/dL, P = 0.01) and HP2-2 (101.0/82.0 mg/dL, P = 0.001) phenotypes. HP2-2 phenotype was also associated with high levels of sCD163 (472.6/418.6 ng/mL, P = 0.02) that were significantly higher among women who subsequently developed PE (511.5/430.8 ng/mL, P = 0.04). Finally, PlGF and sFlt-1 levels presented significantly different patterns between preeclamptic and normal pregnancies, being the strongest association in women with HP2-1 and HP2-2 phenotypes. Conclusion These findings suggest that HP phenotype could be useful in combination with first-trimester inflammatory and angiogenic markers to identify subsets of women with increased risk of PE development since early pregnancy.

Pathobiology of Tennessee 2017 H7N9 low and high pathogenicity avian influenza viruses in commercial broiler breeders and specific pathogen free layer chickens

In March 2017, H7N9 highly pathogenic avian influenza (HPAI) virus was detected in 2 broiler breeder farms in the state of Tennessee, USA. Subsequent surveillance detected the low pathogenicity avian influenza (LPAI) virus precursor in multiple broiler breeder farms and backyard poultry in Tennessee and neighboring states. The pathogenesis of the H7N9 LPAI virus was investigated in commercial broiler breeders, the bird type mostly affected in this outbreak. Infectivity, transmissibility, and pathogenesis of the H7N9 HPAI and LPAI viruses were also studied in 4-week-old specific pathogen free (SPF) leghorn chickens. The mean bird infectious doses (BID50) for the LPAI isolate was 5.6 log10 mean egg infectious dose (EID50) for broiler breeders and 4.3 log10 EID50 for SPF layer chickens, and no transmission to contact-exposed birds was observed. In both bird types, virus shedding was almost exclusively from the oropharyngeal route. These findings suggest sub-optimal adaptation for sustained transmission with the H7N9 LPAI isolate, indicating that factors other than the birds genetic background may explain the epidemiology of the outbreak. The BID50 for the HPAI isolate in SPF layer chickens was more than 2 logs lower (<2 log10 EID50) than the LPAI isolate. Also, the HPAI virus was shed by both the oropharyngeal and cloacal routes and transmitted to contacts. Greater susceptibility and easier transmission of the H7N9 HPAI virus are features of the HP phenotype that could favor the spread of HPAI over LPAI viruses during outbreaks.

The Distribution of Haptoglobin Protein Phenotype in University Gymnastic Players

Purpose: Haptoglobin (Hp) is a plasma protein that is synthesized by the liver and released into circulation and which plays an important role in iron metabolism. Methods: In this study, we investigated the distribution of Hp protein polymorphism in a university male control group and gymnast group as well as its correlation with iron metabolism. The phenotype distribution of Hp protein polymorphism was measured by polyacrylamide gel electrophoresis and peroxidase staining methods, and serum iron metabolism-associated parameters were analyzed automatically. Results: The distribution of Hp protein polymorphism was 14.0%, 42.0% and 44.0% for Hp11, Hp21 and Hp22 phenotypes, respectively. The observed phenotype distribution did not deviate from the Hardy-Weinberg equilibrium. There were no statistically significant differences in phenotype and allele frequencies between the normal control group and the gymnasts. There were significant differences in serum Hp level among each phenotype of Hp gene polymorphism (P < 0.05). In particular, the subjects with the Hp11 phenotype (118.4 ± 33.4 mg/dL) had significantly higher serum Hp concentrations than those with the Hp21 phenotype (79.5 ± 29.5 mg/dL) or the Hp22 phenotype (62.9 ± 23.3 mg/dL). This significance was maintained when the subjects were divided into the control group and the gymnast group. Conclusion: Thus, our data suggest that Hp protein polymorphism significantly affects serum Hp level in the both groups

Redox properties of human hemoglobin in complex with fractionated dimeric and polymeric human haptoglobin

Haptoglobin (Hp) is an abundant and conserved plasma glycoprotein, which binds acellular adult hemoglobin (Hb) dimers with high affinity and facilitates their rapid clearance from circulation after hemolysis. Humans possess three main phenotypes of Hp, designated Hp 1-1, Hp 2-1, and Hp 2-2. These variants exhibit diverse structural configurations and have been reported to be functionally nonequivalent. We have investigated the functional and redox properties of Hb–Hp complexes prepared using commercially fractionated Hp and found that all forms exhibit similar behavior. The rate of Hb dimer binding to Hp occurs with bimolecular rate constants of ~0.9μM−1 s−1, irrespective of the type of Hp assayed. Although Hp binding does accelerate the observed rate of HbO2 autoxidation by dissociating Hb tetramers into dimers, the rate observed for these bound dimers is three- to fourfold slower than that of Hb dimers free in solution. Co-incubation of ferric Hb with any form of Hp inhibits heme loss to below detectable levels. Intrinsic redox potentials (E1/2) of the ferric/ferrous pair of each Hb–Hp complex are similar, varying from +54 to +59mV (vs NHE), and are essentially the same as reported by us previously for Hb–Hp complexes prepared from unfractionated Hp. All Hb–Hp complexes generate similar high amounts of ferryl Hb after exposure to hydrogen peroxide. Electron paramagnetic resonance data indicate that the yields of protein-based radicals during this process are approximately 4 to 5% and are unaffected by the variant of Hp assayed. These data indicate that the Hp fractions examined are equivalent to one another with respect to Hb binding and associated stability and redox properties and that this result should be taken into account in the design of phenotype-specific Hp therapeutics aimed at countering Hb-mediated vascular disease.

Association of haptoglobin phenotypes with serum levels of IgE and IgA in allergic rhinitis patients.

Allergic rhinitis (AR) is an allergic disorder of the nasal tissue that underlies diseases such as sinusitis, otits and asthma. Different predisposing factors including immunological and non-immunological factors contribute to the disease pathogenesis. To investigate association of haptoglobin (Hp) phenotypes (Hp1-1, 2-1 and 2-2) with serum immunoglobulins A and E levels in patients suffering from AR in comparison with healthy individuals. Two hundred and forty patients and 240 healthy individual entered in this case-control study. Serum levels of IgE and IgA were measured and haptoglobulin phenotypes were determined by electrophoresis. The results were evaluated by χ2 statistical test using SPSS software. Serum electrophoresis showed that the distribution of haptoglobin phenotypes of Hp1-1, Hp2-1 and Hp2-2 among 240 patients were 11.3%, 37.9% and 50.8%, respectively. The distribution of different haptoglobin phenotypes in healthy controls were 88.7%, 36.6% and 54.7%, respectively. However, the difference between patients and controls was not statistically significant (p=0.136). The mean of IgE level was significantly higher in patients than controls in association with all three phenotypes (p<0.001). Mean of IgA serum level was also significantly different between case and control groups for Hp1-1 (p<0.048) and Hp2-2 phenotypes (p<0.027). We conclude that there is an association of all three haptoglobin phenotypes with IgE level. Hp1-1 and Hp2-2 phenotypes showed association with IgA in allergic rhinitis, as well. However, we cannot solely attribute these associations to the pathogenesis of allergic rhinitis.

PP159. In women with previous pregnancy hypertension, cardiovascular risk biomarkers may be modulated by haptoglobin genotype

Preeclampsia may affect the risk for future cardiovascular disease. Haptoglobin (Hp), an acute phase protein with genetic polymorphism (Hp1.1, 2.1 and 2.2) synthesized in the hepatocyte and in many tissues, may modulate the risk through the antioxidant and anti-inflammatory differential effects of their genotypes. Evaluate some parameters of cardiovascular risk in association with genetic polymorphism of Hp in women with previous preeclampsia (HBP) compared to healthy women during gestation (NBP). We studied 352 women aged 35±5.48 current year, taking these, 165 presented previous preeclampsia, 2-14 (±6.6) years ago. Genetic polymorphism of Hp was determined from plasma by electrophoresis. The different circulating biomarkers, myeloperoxidase ng/mL (MPO) and nitrates and nitrites (nmol/ml) by ELISA, transaminases - AST and ALT (U/L) and apolipoprotein A and B (mg/dL), uric acid (mg/dl) hs-CRP (mg/L) were determined by conventional methods as well as blood pressure (BP) and anthropometric parameters BMI and hip and waist circumference (WC).Statistical methods were Chi-square, ANOVA (Bonferroni) and t-Student. There were no differences in the distribution of phenotypes of Hp between NBP and those with previous hypertension in pregnancy. There were differences between NBP and HBP in the following parameters: Systolic BP (118.9±13.4 vs 135.0±16.5, p<0.001); Diastolic BP (72.2±10.1 vs 85.9±12.0 p<0.001); MPO (62.3±30.9 vs 85.7±39.4, p=0.020); Nitrite (10.1±3.8 vs 19.1±7.0, p<0.001); ALT (18.0±8.0 vs 22.5±12.9, p=0.016); BMI (25.4±4.1 vs 27.1±4.8, p=0.031); WC (82.8±9.9 vs 89.5±15.6, p=0.002); Apo B (0.6±0.1 vs 0.6±0.1, p=0.023). Those values vary with the genotypes of Hp and were observed Hp 1.1 and 2.1 in NBP and HBP respectively: [Systolic BP 119.2±13.7 vs 134.7±18.3 (p<0.001); Diastolic BP (72.8±11.9 vs 86.2±19.4 p<0.001); MPO (57.9±32.5 vs 94.2±42.1, p=0.008); Nitrites (9.6±3.2 vs 20.0±8.5, p<0.001); ALT(17.0±7.2 vs 20.4±8.0, p=0.033); WC (82.4±10.0 vs 90.8±17.6, p=0.004); Apo A (0.9±0.2 vs 1.0±0.2, p=0.011)] and Hp 2.2 in NBP and HBP respectively: [Systolic BP 118.2±13.1 vs 135.6±12.8 (p<0.001); Diastolic BP (70.9±7.2 vs 85.5±16.3 p<0.001); Nitrites (11.5±5.1 vs 18.0±4.4, p<0.001)]. Women with previous hypertension during pregnancy, presented significant differences in some classic cardiovascular risk biomarkers as well as in some others, associated with the inflammatory process, whose variation may be modulated by haptoglobin functional genetic polymorphism. The history of hypertensive disease in pregnancy may be relevant, in association with these biomarkers to the prevention of cardiovascular disease in particular of postmenopausal women.

Human haptoglobin phenotypes and concentration determination by nanogold-enhancedelectrochemical impedance spectroscopy

Haptoglobin (Hp) is an acute phase protein that binds free hemoglobin (Hb), preventingHb-induced oxidative damage in the vascular system. There are three phenotypes in humanHp, whose heterogeneous polymorphic structures and varying concentrations in plasmahave been attributed to the cause of diseases and outcome of clinical treatments.Different phenotypes of Hp may be composed of the same subunits but different copynumbers, rendering their determination difficult by a single procedure. In this study,we have developed a simple, fast, reliable and sensitive method, using label-freenanogold-modified bioprobes coupled with self-development electrochemical impedancespectroscopy (EIS). By this method, probe surface charge transfer resistance isdetected. The relative charge transfer resistance ratios for Hp 1-1, Hp 2-1 and Hp2-2 were characterized. We were able to determine protein size difference within3 nm, and the linear region of the calibration curve for Hp levels in the range of90 pg ml − 1 and90 µg ml − 1 (∼1 fM to 1 pM). We surmise that similar approaches can be used to investigate proteinpolymorphism and altered protein–protein interaction associated with diseases.

On-line microheterogeneity analysis and rapid phenotyping of haptoglobin by capillary electrophoresis using sodium dodecyl sulfate as additive

To improve the detection sensitivity and determine phenotypes of haptoglobin (Hp), a prefilling technique was developed and tested in capillary electrophoresis (CE) with UV–vis absorbance detection. Adding 0.01% sodium dodecyl sulfate (SDS) to the protein sample and 0.1% SDS to the prefilling buffer solution, on-line stacking and microheterogeneity separation of Hp were achieved. In addition, the influences of pH, buffer concentration, sample and prefilling buffer SDS concentration upon resolution were examined. Under optimized conditions, Hp-microheterogeneity was well resolved and two phenotypes of Hp (Hp 1-1 and Hp 2-2) were differentiated. This method was applied to the analysis of sera from normal individuals and β-Thalassemia patients. After the depletion of albumin (HSA) and immunoglobulin G (IgG), this method allowed to determine two phenotypes in different individuals and to detect the decrease of Hp in β-Thalassemia patients. Featuring high efficiency, speed and simplicity, the proposed method shows great potential for use in clinical diagnosis and proteome research.

A Unique Loop Extension in the Serine Protease Domain of Haptoglobin Is Essential for CD163 Recognition of the Haptoglobin-Hemoglobin Complex

Haptoglobin and haptoglobin-related protein are homologous hemoglobin-binding proteins consisting of a complement control repeat (alpha-chain) and a serine protease domain (beta-chain). Haptoglobin-hemoglobin complex formation promotes high affinity binding of hemoglobin to the macrophage scavenger receptor CD163 leading to endocytosis and degradation of the haptoglobin-hemoglobin complex. In contrast, complex formation between haptoglobin-related protein and hemoglobin does not promote high affinity interaction with CD163. To define structural components of haptoglobin important for CD163 recognition, we exploited this functional difference to design and analyze recombinant haptoglobin/haptoglobin-related protein chimeras complexed to hemoglobin. These data revealed that only the beta-chain of haptoglobin is involved in receptor recognition. Substitution of 4 closely spaced amino acid residues of the haptoglobin beta-chain (valine 259, glutamate 261, lysine 262, and threonine 264) abrogated the high affinity receptor binding. The 4 residues are encompassed by a part of the primary structure not present in other serine protease domain proteins. Structural modeling based on the well characterized serine protease domain fold suggests that this sequence represents a loop extension unique for haptoglobin and haptoglobin-related protein. A synthetic peptide representing the haptoglobin loop sequence exhibited a pronounced inhibitory effect on receptor binding of haptoglobin-hemoglobin.

Effective NSAID treatment indicates that hyperprostaglandinism is affecting the clinical severity of childhood hypophosphatasia

BackgroundHypophosphatasia (HP) is an inborn error of bone metabolism characterized by a genetic defect in the gene encoding the tissue-nonspecific alkaline phosphatase (TNSALP). There is a lack of knowledge as to how the variability and clinical severity of the HP phenotype (especially pain and walking impairment) are related to metabolic disturbances or impairments, subsequent to the molecular defect.MethodsWe analyzed the changes in clinical symptoms and the prostaglandin (PG) metabolism in response to treatment with non-steroidal anti-inflammatory drugs (NSAIDs) in six children affected by childhood HP. In addition, by exposing HP fibroblasts to pyridoxal phosphate and/or calcium pyrophosphate in vitro, we analyzed whether the alterations in PG levels are sequelae related to the metabolic defect.ResultsChildhood HP patients, who often complain about pain in the lower limbs without evident fractures, have systemic hyperprostaglandinism. Symptomatic anti-inflammatory treatment with NSAIDs significantly improved pain-associated physical impairment. Calcium pyrophosphate, but not pyridoxal phosphate, induced cyclooxygenase-2 (COX-2) gene expression and PG production in HP and normal fibroblasts in vitro.ConclusionClinical features of childhood HP related to pain in the lower legs may be, at least in part, sequelae related to elevated PG levels, secondary to the primary metabolic defect. Consequently, NSAID treatment does improve the clinical features of childhood HP.

Is Delayed Childbearing Changing Gene Frequencies in Western Populations?

Experimental data and clinical observations suggest that delaying childbearing influences the biology of the mother-fetus relationship, with a negative effect on fetal development and predisposition to severe diseases such as type 1 diabetes. We reason that advanced maternal age may influence intrauterine selection, favoring genotypes that are more adapted to the intrauterine environment of less young women. In the present study we have investigated the relationship of maternal age to HP genotype and PGM1-Rh area (chromosome 1) that have been previously found to be associated with fertility and developmental parameters. HP phenotype was determined in 679 consecutive puerperae from the population of central Italy. PGM1 phenotype and Rh C phenotype were determined in 222 puerperae and 200 newborns. The HP 1,1 phenotype decreases and the HP 2,2 phenotype increases with maternal age. The proportion of phenotypes carrying both the Rh C and PGM1*1 alleles is much higher in puerperae older than 36 years than in puerperae of age 22 years. The frequency of the PGM1*1-Rh C haplotype increases and the frequency of the PGM1*2-Rh C haplotype decreases with maternal age. The changes in these genetic systems with advancing maternal age are similar in mothers and newborns. The delay of childbearing age, associated in Western countries with the fertility transition in addition to detrimental effects on intrauterine development and increased susceptibility to severe disorders, could bring about changes in the genetic composition of a population.

Haptoglobin phenotypes and malaria infection in pregnant women at delivery in western Cameroon

Plasmodium falciparum-infected erythrocytes have been reported to sequester in the placenta by adhering to chondroitin 4-sulfate during pregnancy. Earlier studies have highlighted higher susceptibility of primigravidae to P. falciparum compared to multigravidae living within the same endemic areas. The haptoglobin phenotype (Hp1-1) has been associated with susceptibility to severe P. falciparum malaria and the presence of Hp in human endometrium has been reported. The possible role of different Hp phenotypes in susceptibility to or protection from placental infection by P. falciparum in both primigravid and multigravid women at delivery in western Cameroon was investigated in this study. Only the three major haptoglobin phenotypes; Hp1-1, Hp2-1 and Hp2-2, were found in the study population with the Hp1-1 phenotype being the predominant (53%). There was no significant difference in the distribution of the three Hp phenotypes between the two gravidity groups. Women carrying the Hp1-1 phenotype had higher parasite prevalences in both peripheral blood (21.6% against 9.1%) and placentas (42% against 16.7%) when compared to those with the Hp2-2 phenotype. The difference in the parasite density between women carrying the Hp1-1 and Hp2-2 phenotypes was statistically significant for placental infection ( P=0.001) but not for maternal peripheral blood infection. Placental parasitaemias without peripheral blood parasitaemias were detected in 42.6% of all the P. falciparum positive women while 27.7% of the women had peripheral blood parasitaemias in the absence of placental infection and 29.8% of the women had both placental and peripheral blood parasitaemias. A statistically significant difference was observed between the primigravidae and multigravidae in the parasite density in placental biopsies ( P=0.02) but not for maternal peripheral blood parasitaemia. Our data suggest that the Hp1-1 phenotype may play a role in susceptibility to placental infection by P. falciparum during pregnancy.

Acquisition of HP phenotype and alterations in the activity of catalase of in vitro transformed cells of different origin in the dynamics of in vivo tumor progression.

Acquisition of HP phenotype and alterations in the activity of catalase of in vitro transformed cells of different origin in the dynamics of in vivo tumor progression.

The Protein Polymorphism of Haptoglobin in Korean Elite Athletes

Objective: To investigate protein polymorphism of the haptoglobin (Hp) and the relationship between Hp phenotypes and anthropometric or biochemical parameters in elite Korean male athletes. Materials and Methods: Serum samples were collected from 120 Korean male elite athletes. The Hp phenotypes were determined by polyacrylamide gel electrophoresis, followed by peroxidase staining. Then anthropometric or biochemical measurements were made: body composition, blood pressures, ventilatory responses, cholesterol (total, LDL cholesterol and HDL cholesterol), triglyceride, apolipoprotein A1, lipoprotein (a), creatine phosphokinase and lactate dehydrogenase. Results: The gene frequencies of the Hp1-1, Hp2-1 and Hp2-2 phenotypes in Korean male athletes were 12, 37 and 51%, respectively; this polymorphism was significantly associated with the VO_2max index in the athletes. An excess of the Hp1 allele was also observed in marathon runners compared with the other sporting activities, although it did not have any statistical significance. Conclusion: Hp polymorphism exists in elite Korean male athletes and Hp phenotype may be a useful marker for endurance performance in these male athletes.

HP, TF and GC Phenotype and Allele Frequencies in Four South Indian Population Groups

HP, TF and GC serum protein polymorphisms were typed on the Kamma caste group as well as on three Muslim groups (Dawoodi Bohara, Sunni, Shia) from the Visakhapatnam area in Andhra Pradesh (South In...