Hemoglobin D-Punjab: origin, distribution and laboratory diagnosis

Torres, Lidiane de Souza; Okumura, Jéssika Viviani; Silva, Danilo Grünig Humberto da; Bonini-Domingos, Cláudia Regina

doi:10.1016/j.bjhh.2015.02.007

Cited by 51 publications

(39 citation statements)

References 38 publications

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“…As Hb S concentration is a determinant factor for the SCD clinical severity, double heterozygous genotypes usually, but not always, are less clinically severe than Hb SS [3,37]. However, the similarity found between Hb SS and Hb SD groups may be a result from the Hb D properties to increase the polymerization rate of the Hb S. The mutation responsible for Hb D ( HBB :c.364G>C) occurs in an interaction site between Hb S molecules and possibly the amino acid change (Glu→Gln) encourages this interaction, promoting the polymerization process and the erythrocyte sickling [38,39]. …”

Section: Discussionmentioning

confidence: 99%

Inflammation in Sickle Cell Disease: Differential and Down-Expressed Plasma Levels of Annexin A1 Protein

et al. 2016

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Sickle cell disease (SCD) is an inherited hemolytic anemia whose pathophysiology is driven by polymerization of the hemoglobin S (Hb S), leading to hemolysis and vaso-occlusive events. Inflammation is a fundamental component in these processes and a continuous inflammatory stimulus can lead to tissue damages. Thus, pro-resolving pathways emerge in order to restore the homeostasis. For example there is the annexin A1 (ANXA1), an endogenous anti-inflammatory protein involved in reducing neutrophil-endothelial interactions, accelerating neutrophil apoptosis and stimulating macrophage efferocytosis. We investigated the expression of ANXA1 in plasma of SCD patients and its relation with anemic, hemolytic and inflammatory parameters of the disease. Three SCD genotypes were considered: the homozygous inheritance for Hb S (Hb SS) and the association between Hb S and the hemoglobin variants D-Punjab (Hb SD) and C (Hb SC). ANXA1 and proinflammatory cytokines were quantified by ELISA in plasma of SCD patients and control individuals without hemoglobinopathies. Hematological and biochemical parameters were analyzed by flow cytometry and spectrophotometer. The plasma levels of ANXA1 were about three-fold lesser in SCD patients compared to the control group, and within the SCD genotypes the most elevated levels were found in Hb SS individuals (approximately three-fold higher). Proinflammatory cytokines were higher in SCD groups than in the control individuals. Anemic and hemolytic markers were higher in Hb SS and Hb SD genotypes compared to Hb SC patients. White blood cells and platelets count were higher in Hb SS genotype and were positively correlated to ANXA1 levels. We found that ANXA1 is down-regulated and differentially expressed within the SCD genotypes. Its expression seems to depend on the inflammatory, hemolytic and vaso-occlusive characteristics of the diseased. These data may lead to new biological targets for therapeutic intervention in SCD.

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Section: Discussionmentioning

confidence: 99%

Inflammation in Sickle Cell Disease: Differential and Down-Expressed Plasma Levels of Annexin A1 Protein

et al. 2016

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“…This mutation is generally asymptomatic but may occasionally cause moderate hemolytic anemia, similar to the manifestations of sickle cell anemia when associated with other hemoglobin variants, such as HbS or β-thalassemia mutations. Its initial distribution suggests that it is more prevalent in the central region of Asia, but due to migration, it can be found in several other regions [50]. …”

Section: Discussionmentioning

confidence: 99%

Investigation of mutations in the HBB gene using the 1,000 genomes database

et al. 2017

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Mutations in the HBB gene are responsible for several serious hemoglobinopathies, such as sickle cell anemia and β-thalassemia. Sickle cell anemia is one of the most common monogenic diseases worldwide. Due to its prevalence, diverse strategies have been developed for a better understanding of its molecular mechanisms. In silico analysis has been increasingly used to investigate the genotype-phenotype relationship of many diseases, and the sequences of healthy individuals deposited in the 1,000 Genomes database appear to be an excellent tool for such analysis. The objective of this study is to analyze the variations in the HBB gene in the 1,000 Genomes database, to describe the mutation frequencies in the different population groups, and to investigate the pattern of pathogenicity. The computational tool SNPEFF was used to align the data from 2,504 samples of the 1,000 Genomes database with the HG19 genome reference. The pathogenicity of each amino acid change was investigated using the databases CLINVAR, dbSNP and HbVar and five different predictors. Twenty different mutations were found in 209 healthy individuals. The African group had the highest number of individuals with mutations, and the European group had the lowest number. Thus, it is concluded that approximately 8.3% of phenotypically healthy individuals from the 1,000 Genomes database have some mutation in the HBB gene. The frequency of mutated genes was estimated at 0.042, so that the expected frequency of being homozygous or compound heterozygous for these variants in the next generation is approximately 0.002. In total, 193 subjects had a non-synonymous mutation, which 186 (7.4%) have a deleterious mutation. Considering that the 1,000 Genomes database is representative of the world’s population, it can be estimated that fourteen out of every 10,000 individuals in the world will have a hemoglobinopathy in the next generation.

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“…Association with HbS and Thalassemia also occur. [20] .MCV was lower in HbE/ β Thalassemia compared to β Thalassemia, HbE trait and SCT in the ascending order . A similar pattern has been described by Vani and others.…”

Section: Discussionmentioning

confidence: 85%

HbA2 and Fetal haemoglobin in the diagnosis of Thalassemia and Hemoglobinopathies

Venkatachala

Rajendran

2017

APALM

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Background: Hemoglobin (Hb) disorders which include hemoglobinopathies and Thalassemia affect 7% of the world population. Capillary electrophoresis is useful for screening and follow up of Hb disorders . Aim:To evaluate HbA2 and HbF (fetalhemoglobin) in the diagnosis of Thalassemia and hemoglobinopathies.Material and Methods: 100 consecutive Capillary Hemoglobin electrophoresis done as a part of screening programme for Hb disorders from Jan2016 to june 2016 was included in the study. Children <1 yr of age and individuals with recent blood transfusion were excluded . Hb, RBC count and MCV were recorded.Results: Of the 100 Hb electrophoresis performed, 57 normal and 43 abnormal patterns were seen. Among the abnormal Hb patterns, β thalassemia trait (βTT) was the most common constituting 58.2% followed by Sickle cell (HbS) trait(11.7%), HbE trait(9.3%) and HbE/ β Thalassemia (7.0%). The HbA2 levels in normal, βTT, Sickle cell trait , HbE trait and HbE/ β thalassemia were 2.12%(SD 0.5), 4.9%(SD 0.62), 3.28%(SD 0.43), 3.98%(SD 0.67) respectively . The difference in HbA2 were significant (p value <0.0001).The difference in HbA2 levels between HbE trait and HbE disease was also significant (p value 0.036).Based on the HbF levels Sickle cell hemoglobinopathy was further classified. Conclusion:The difference in HbA2 levels in normal subjects, Thalassemia and hemoglobinopathies are statistically significant. The percentage of HbF in sickle cell gives information about coexisting hemoglobin disorder. In HbEhemoglobinopathy, HbA2 along with HbF identifies a specific group HbE/ β Thalassemia which often needs clinical intervention.

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Hemoglobin D-Punjab: origin, distribution and laboratory diagnosis

Cited by 51 publications

References 38 publications

Inflammation in Sickle Cell Disease: Differential and Down-Expressed Plasma Levels of Annexin A1 Protein

Inflammation in Sickle Cell Disease: Differential and Down-Expressed Plasma Levels of Annexin A1 Protein

Investigation of mutations in the HBB gene using the 1,000 genomes database

HbA2 and Fetal haemoglobin in the diagnosis of Thalassemia and Hemoglobinopathies

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