Hemoglobin E: Distribution and population dynamics

Hemoglobin E, an anomaly of the -chain of human hemoglobin, is widely distributed in Southeast Asia and adjacent areas. In some populations of Southeast Asia the frequency of the gene responsible for the production of HbE reaches values near 0.3. In view of the probable disadvantage of the HbE homozygote and the certain disadvantage of the double heterozygote for the HbE and -thalassemia genes an advantage of the heterozygote has to be postulated in order to explain the high gene frequencies. There is some evidence for and against malaria protection being the factor conveying heterozygote advantage. Data concerning genotype fitnesses in the triallelic system involving HbA, HbE and -thalassemia are scanty. Crude fitness data based on clinical observations and equilibrium calculations indicate that the system is unstable. Dynamic models of the three genes suggest that the HbE gene is replacing the -thalassemia gene in most Southeast Asian populations. The distribution of HbE and that of the austroasiatic group of languages are similar. This and several other aspects of the geographic and ethnic distribution of HbE are discussed in the last section of this review.     

Hemoglobin E disorder: Newborn screening program

Hemoglobin E (Hb E) disorder is an important kind of hemoglobinopathy. It can be seen around the world with the highest prevalence in Southeast Asia. The screening for this disorder becomes the public health policies in many countries. The screening can be performed in several population groups. The newborn screening program for Hb E disorder is an important issue in pediatric genetics. In this brief review, the author discusses on important laboratory tests for screening for Hb E disorder in newborn.     

西藏拉萨地区藏族儿童血红蛋白类型和一例血红蛋白E的化学结构分析

本文报道480例西藏拉萨地区藏族儿童的血红蛋白类型,除发现一例慢速β链Hb变异体之外,其余均无异常。对该异常者Hb的化学结构进行分析,确证为HbE[β~(26(B8))Glu→Lys]。此为我国藏族人群中首次发现。     

Hemoglobin E distribution in ten endogamous population groups of Assam, India

Previous studies have reported a high incidence of hemoglobin E (HbE) in Northeast Indian populations. In the present study 10 endogamous populations of Assam belonging to two racial groups, Caucasoid and Mongoloid, were examined. The frequency of HbE gene (Hb beta E) in the Caucasoid caste populations is around 0.1, whereas the gene is highly prevalent in the Mongoloid populations, frequencies ranging between 0.2 and 0.6. Predominance of Hb beta E in the Tibeto-Burman speakers is contrary to observations made in Southeast Asia, where an association between Austro-Asiatic speakers and high prevalence of HbE exist. The highest occurrence of the gene in this area, which is on the far end of the proposed centre of distribution in Northern Kampuchea and Northeast Thailand, is also a deviation from the expected pattern of gene distribution. It is speculated that Hb beta E in the Tibeto-Burman populations of Assam arose by an independent mutation which contributed to the high frequencies of Hb beta E in the Northeast Indian populations.     

Hemoglobin E: report of the first 2 cases in French subjects

Hemoglobin E has been discovered casually in the blood of two French donors: one coming from the Alsace region, the other one coming from the Champagne region. In the two cases, the hemoglobin E is in an heterozygote state and takes the place of 33 per cent of the total haemoglobin in the first and 24 per cent in the second. We investigated in their families and found that other members of these families had hemoglobin E. Each time, it was associated with a microcytosis and polycythaemia without anemy or iron deficiency. The red cells morphology shows many microspherocytes and target-cells. There is no relationship between these two families and the research of an asiatic antecedent proved negative. These two observations give a supplementary proof that the geographic repartition of the hemoglobin E is larger than what we read in the first publications and shows the interest to study the hemoglobin of unexplained polycythaemia with microcytes in the blood of blood donors.     

Hemoglobin E: a common hemoglobinopathy among children of Southeast Asian origin.

With the recent immigration of Southeast Asians to Canada, hemoglobin E has become a frequent diagnosis. The clinical and hematologic findings in 42 children (mean age 4.3 years) with hemoglobin E are presented. There were 33 heterozygotes (having hemoglobin E trait), 6 homozygotes (having hemoglobin EE) and 3 double heterozygotes (having hemoglobin E-beta-thalassemia). The heterozygotes had low-normal hemoglobin levels and mean corpuscular volumes; coexisting iron deficiency, present in 62% of these children, resulted in substantially lower hemoglobin levels, very low mean corpuscular volumes and lower than expected levels of hemoglobin E on electrophoresis. The children with hemoglobin EE were only slightly anemic, but those with hemoglobin E-beta-thalassemia had severe anemia and required long-term transfusion therapy. Nutritional factors and parasitic infestations were the main causes of iron depletion, which was common, particularly in children less than 2 years old (87%). Physicians of patients of Southeast Asian origin should be aware of the clinical and hematologic presentation of these hemoglobinopathies.     

Epistatic Interactions between Apolipoprotein E and Hemoglobin S Genes in Regulation of Malaria Parasitemia

Apolipoprotein E is a monomeric protein secreted by the liver and responsible for the transport of plasma cholesterol and triglycerides. The APOE gene encodes 3 isoforms Ɛ4, Ɛ3 and Ɛ2 with APOE Ɛ4 associated with higher plasma cholesterol levels and increased pathogenesis in several infectious diseases (HIV, HSV). Given that cholesterol is an important nutrient for malaria parasites, we examined whether APOE Ɛ4 was a risk factor for Plasmodium infection, in terms of prevalence or parasite density. A cross sectional survey was performed in 508 children aged 1 to 12 years in Gabon during the wet season. Children were screened for Plasmodium spp. infection, APOE and hemoglobin S (HbS) polymorphisms. Median parasite densities were significantly higher in APOE Ɛ4 children for Plasmodium spp. densities compared to non-APOE Ɛ4 children. When stratified for HbS polymorphisms, median Plasmodium spp. densities were significantly higher in HbAA children if they had an APOE Ɛ4 allele compared to those without an APOE Ɛ4 allele. When considering non-APOE Ɛ4 children, there was no quantitative reduction of Plasmodium spp. parasite densities for HbAS compared to HbAA phenotypes. No influence of APOE Ɛ4 on successful Plasmodium liver cell invasion was detected by multiplicity of infection. These results show that the APOE Ɛ4 allele is associated with higher median malaria parasite densities in children likely due to the importance of cholesterol availability to parasite growth and replication. Results suggest an epistatic interaction between APOE and HbS genes such that sickle cell trait only had an effect on parasite density in APOE Ɛ4 children. This suggests a linked pathway of regulation of parasite density involving expression of these genes. These findings have significance for understanding host determinants of regulation of malaria parasite density, the design of clinical trials as well as studies of co-infection with Plasmodium and other pathogens.     

Hemoglobin polymorphism in Equus przewalskii and E. caballus analyzed by isoelectric focusing.

1. Through the use of isoelectric focusing and peptide analysis, the hemoglobins of Przewalski's horse. Equus przewalskii and the domestic horse, E. caballus have been compared. 2. Przewalski's horses have two separate alpha-globin chain polymorphisms similar to domestic horses. Each hemoglobin phenotype could be accurately determined by isoelectric focusing. 3. Confirmation of the electrofocusing hemoglobin determinations was made by comparison to amino acid composition analyses of purified tryptic peptides and by analysis of the rare hemoglobins phenotypes observed in a family of Norwegian trotting horses. 4. Hemoglobin genotypes of fifteen Przewalski's horses were determined and inheritance of hemoglobin haplotypes has been observed.     

Hemoglobin E in Europeans: further evidence for multiple origins of the beta E-globin gene

We have determined haplotypes for the known restriction site polymorphisms in the beta-globin gene cluster in two families of European ancestry containing individuals who are heterozygous for hemoglobin E. In both families, the beta E mutation is associated with a haplotype not previously found among the haplotypes of beta E chromosomes in Southeast Asia. Moreover, in one family, the mutation is present in a beta-gene framework not found in beta E chromosomes of Southeast Asia. These data provide further evidence of multiple independent origins of the beta E mutation in human populations.     

戊二醛聚合对猪、牛和人血红蛋白免疫学特性的影响

猪、牛、人血红蛋白或其相应的戊二醛聚合体分别经皮下或腹腔多次免疫小鼠,ELISA检测抗血清IgG滴度;免疫印迹法分别检测小鼠抗猪、牛、人血红蛋白或其相应的戊二醛聚合体IgG与猪、牛、人血红蛋白或其相应的戊二醛聚合体之间的交叉反应,探讨戊二醛聚合对不同种类血红蛋白免疫学特性的影响.结果表明:猪、牛、人血红蛋白的免疫原性均...     

Hemoglobin abnormalities

Summary In order to evaluate the polymorphism of hemoglobin in a population of Equatorial Africa, we undertook a prospective study of 146 births at a rural maternity hospital close to Brazzaville (P.R. Congo). This showed among the mothers 31 (22%) carriers of the sickle cell trait (AS), six with mutation, and two with -thalassemia triat. Among the children, 27 (18.5%) had sickle cell trait and one had sickle cell homozygosity. The frequency of the HbF Sardinia trait was 7.5%. This and other studies suggested a dilution gradient from Europe to Africa. Hemoglobin Bart's could be visually detected in 23.3% of the new-born babies. We attempted to distinguish between those infants with a high level of Hb Bart's (Bart's ++ group: 13.7%) and a group with a detectable Hb Bart's level that in our experimental conditions is between 1 and 2% (Bart's + group: 9.6%). Mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) were 88.6 ±5.7 fl and 29.0±2.1 pg in the Bart's ++ group; 94.5±10.9 fl and 30.6±4.1 pg in the Bart's + group; whereas they were 101.0±8.7 fl and 33.9±2.5 pg in the control group. Since iron dificiencies are very rare in new-borns and selecting according to published data on black people as homozygous -thalassemia of the type I (-/-), individuals of the Bart's ++ group whose MCV was below 95 fl and MCV below 30 pg, the gene frequency is estimated to be 34% and that of heterozygotes (-/) 45%. These high frequencies were confirmed in AS mothers: 45% showed a significant decrease of the S fraction.