Showing papers on "Hemoglobin A2 published in 2014"

In vivo activation of the human δ-globin gene: the therapeutic potential in β-thalassemic mice

Abstract: β-thalassemia and sickle cell disease are widespread fatal genetic diseases. None of the existing clinical treatments provides a solution for all patients. Two main strategies for treatment are currently being investigated: (i) gene transfer of a normal β-globin gene; (ii) reactivation of the endogenous γ-globin gene. To date, neither approach has led to a satisfactory, commonly accepted standard of care. The δ-globin gene produces the δ-globin of hemoglobin A2. Although expressed at a low level, hemoglobin A2 is fully functional and could be a valid substitute of hemoglobin A in β-thalassemia, as well as an anti-sickling agent in sickle cell disease. Previous in vitro results suggested the feasibility of transcriptional activation of the human δ-globin gene promoter by inserting a Kruppel-like factor 1 binding site. We evaluated the activation of the Kruppel-like factor 1 containing δ-globin gene in vivo in transgenic mice. To evaluate the therapeutic potential we crossed the transgenic mice carrying a single copy activated δ-globin gene with a mouse model of β-thalassemia intermedia. We show that the human δ-globin gene can be activated in vivo in a stage- and tissue-specific fashion simply by the insertion of a Kruppel-like factor 1 binding site into the promoter. In addition the activated δ-globin gene gives rise to a robust increase of the hemoglobin level in β-thalassemic mice, effectively improving the thalassemia phenotype. These results demonstrate, for the first time, the therapeutic potential of the δ-globin gene for treating severe hemoglobin disorders which could lead to novel approaches, not involving gene addition or reactivation, to the cure of β-hemoglobinopathies.

The genetics of hemoglobin A2 regulation in sickle cell anemia.

Abstract: Hemoglobin A2, a tetramer of α- and δ-globin chains, comprises less than 3% of total hemoglobin in normal adults. In northern Europeans, single nucleotide polymorphisms (SNPs) in the HBS1L-MYB locus on chromosome 6q and the HBB cluster on chromosome 11p were associated with HbA2 levels. We examined the genetic basis of HbA2 variability in sickle cell anemia using genome-wide association studies. HbA2 levels were associated with SNPs in the HBS1L-MYB interval and SNPs in BCL11A. These effects are mediated by the association of these loci with γ-globin gene expression and fetal hemoglobin (HbF) levels. The association of polymorphisms downstream of the β-globin gene (HBB) cluster on chromosome 11 with HbA2 was not mediated by HbF. In sickle cell anemia, levels of HbA2 appear to be modulated by trans-acting genes that affect HBG expression and perhaps also elements within the β-globin gene cluster. HbA2 is expressed pancellularly and can inhibit HbS polymerization. It remains to be seen if genetic regulators of HbA2 can be exploited for therapeutic purposes. Am. J. Hematol. 89:1019–1023, 2014. © 2014 Wiley Periodicals, Inc.

Delineation of the molecular basis of borderline hemoglobin A2 in Chinese individuals

Abstract: Background The “gray zone” of borderline hemoglobin A 2 (Hb A 2 ) may be present in a large section of the population, especially in countries where thalassemia is common. However, very little is currently known of the molecular basis of borderline Hb A 2 in Chinese individuals. Method In this study, we performed a comprehensive analysis of the globin genotypes and KLF1 gene mutations associated with borderline Hb A 2 in 165 Chinese subjects. Result Fifteen (9.1%) were positive for a molecular defect in the α-,β-globin genes, of whom, α-thalassemia mutations and α-globin gene triplication were found in eleven cases, accounting for about 73.3% of these globin gene defects. Twenty (12.1%) were positive for a molecular defect in the KLF1 gene. Eight different mutations were identified, six of which are here reported for the first time. The most common is the G176AfsX179 mutation, accounting for 50% of the total. Conclusions The molecular characterization of borderline Hb A 2 in Chinese individuals is significantly different than in Italian population. Our data is conductive to provision of genetic counseling for Chinese individuals with borderline Hb A 2 .

Molecular diagnosis for a novel deletion mutation of α thalassemia

Abstract: OBJECTIVE To raise awareness of the pathogenesis and diagnosis of thalassemia by reporting one case of α thalassemia patient with a large deletion fragment and analyzing the pedigree. METHODS Firstly, blood cells and hemoglobin electrophoresis analysis were used for screening of thalassemia, and then three common kinds of deletional α thalassemia in Chinese was detected by Gap-PCR, three common kinds of non- deletional α thalassemia and seventeen common mutations of β thalassemia in Chinese were analyzed by using PCR- RDB. The unknown mutation of samples was identified with Multiplex Ligation-dependent Probe Amplification (MLPA) and DNA sequencing. RESULTS The proband female presented with microcytic hypochromic anemia(hemoglobin 71 g/L, mean corpuscular volume 52.4 fl, mean corpuscular hemoglobin 16.1 pg), and hemoglobin A2 1.4%. The identified large deletion fragment length was 21 925 bp, so far which had not been reported in the world and was named -α²¹·⁹. It was registered in USA DNA database and GenBank accession number as KF360979. The genotype of her mother and father and brother were αα/-α²¹·⁹, --(SEA)/-α³·⁷, αα/-α³·⁷ respectively, and the genotype of her and her sister were the same of --(SEA)/-α²¹·⁹. Her husband gene of thalassemia had no mutation, so prenatal diagnosis of thalassemia was not carried out in the pregnant woman. CONCLUSION The discovery of -α(21.9) deletion mutation was enriched the DNA mutation gene database of thalassemia, and had important significance for genetic counseling and thalassemia prenatal diagnosis.

Caracterización de alteraciones en la molécula de hemoglobina en afrodescendientes colombianos

Abstract: Objective: Characterize molecular alterations of hemoglobin in Afro-Colombian subjects, ranging in age from 18 to 50 years. Analyses were conducted via complete blood count, peripheral blood smear, C-Reactive Protein, serum Ferritin, Soluble Transferrin Receptor (sTfR) and electrophoresis. Materials and Methods: A total of 56 subjects were analyzed, 10 men and 46 women. Results: Subjects (from the Aguablanca District in the City of Cali) showed alterations in the hemoglobin chain associated with Hemoglobin S, Hemoglobin C and possible thalassemias due to Fetal Hemoglobin and augmented Hemoglobin A2. Additionally, a small incidence of subclinical deficiencies of iron at different stages was also detected.

Prevalence of beta thalassemia minor, iron deficiency and glucose-6-phosphate dehydrogenase deficiency in Iranian boy's primary schools in Yasuj

Abstract: The prevalence of thalassemia and iron deficiency in Iran varies greatly from area to area. Aims: determination of prevalence of beta thalassemia minor, iron deficiency and glucose 6 phosphate dehydrogenase (G6PD) in yasuj iran. Materials and Methods: Two hundred eighty boy's primary schools were selected. Two ml of blood in EDTA tubes for hematologicals parameters and 4 ml in non anticoagulated tubes for serum iron (SI), total iron binding capacity (TIBC) and serum ferritin (SF) was collected from all participants by antecubital vein puncture. HbA 2 was estimated. Result: MCV≥80fl in 80% and MCV below 80 fl in 20 % of all participants was reported .MCH ≤25 pg, and RBC count ≥ 6× 10 6 /μL were found in 10% and 6 % of participants respectively. Out of all participant 38 (13%) was reported with MCV ≤ 80 fl. Hemoglobin A2 more than 3.5 percent was reported in 17 (6%) and hemoglobin A2 less than 3.5 percent was 21 (7%) of participants. From 280 participants 17 students (6%) were diagnosed as beta thalassemia minor. Out of 280 participants, 39 (13.92%) subjects had SF below 12 ng/ml and 241(86.08%) subject had SF more than 12 ng/ml .The prevalence of G6PD deficiency was reported 12.7%. Conclusion: out of 280 students screened 39 (13.92%) were found to be anaemic, while 17(6%) students were positive for BTM and only 35 (12.5%) students were positive for G6PD deficiency. (Reza Maleki, Ali Shariati, Nooshin Mirzaei, Ali Mirzaei. Prevalence of beta thalassemia minor, iron deficiency and glucose-6-phosphate dehydrogenase deficiency in Iranian boy's primary schools in Yasuj. Life Sci J 2014;11(9s):505-508) (ISSN:1097-8135). http://www.lifesciencesite.com. 99

Characterization of molecular alterations of hemoglobin in Afro-Colombians

Abstract: Objective: Characterize molecular alterations of hemoglobin in Afro-Colombian subjects, ranging in age from 18 to 50 years. Analyses were conducted via complete blood count, peripheral blood smear, C-Reactive Protein, serum Ferritin, Soluble Transferrin Receptor (sTfR) and electrophoresis. Materials and Methods: A total of 56 subjects were analyzed, 10 men and 46 women. Results: Subjects (from the Aguablanca District in the City of Cali) showed alterations in the hemoglobin chain associated with Hemoglobin S, Hemoglobin C and possible thalassemias due to Fetal Hemoglobin and augmented Hemoglobin A2. Additionally, a small incidence of subclinical deficiencies of iron at different stages was also detected.

Quantifying method of hemoglobin f using liquid chromatography

Abstract: PROBLEM TO BE SOLVED: To provide a quantifying method which accurately and reproducibly quantifies hemoglobin F and other hemoglobin such as hemoglobin A2 or the like simultaneously.SOLUTION: In a chromatogram of liquid chromatography, an area from elution peak start time of hemoglobin F to elution end time of the elution peak established in accordance with a certain condition is determined.

Prevalence of Beta Thalassaemia in Jenin Area in Palestine

Abstract: The study intended to determine the frequency of B-Thalassaemia and other abnormal hemoglobins among the major ten Palestinean families using blood samples collected from 263 unrelated individuals belonging to those families. Samples were selected randomly proportional to the size of each family and subjected for Complete Blood Count (CBC), Gel electrophoresis and Chromatographic separation of HbA2. Results showed that elevation of hemoglobin F (Hb-F) was close to that of hemoglobin A2 (Hb-A2) and clearly observed in Aboalrob and Torokman followed by Ziud, Daraghmeh, Jaradat, Amarneh and Qlalweh. Elevation of the combination (Hb-F & A2) was significantly associated with microcytosis (low MCV) and hypochromia (low MCHC). Haemoglobin S (Hb-S) was highly detected in Qalalweh (41%) followed by Noairat (27%), Aboalrob (14%), Zaqzooq (9%) and Amarneh and Zekarneh (5%). Hb-S was significantly associated with low MCH and normal MCV and MCHC. On the other hand, the comparison between Hb Electrophoresis and Ion-exchange Resin laboratory methods, which used for the detection of abnormal hemoglobins revealed significant increase of the detection limit of Hb Electrophoresis than Ion-exchange Resin. The study concluded that the frequency of B Thalassaemia is quietly different among Palestinean families in addition to the presence of Hb-S. Therefore, it was strongly recommended establish a social protocol for marriage accompanied with medical investigation and supervision to reduce this risk. Also, the study recommend to apply Hb Electrophoresis since it is more reliable.

Talasemi taramasinda Agilent 1100 (Chromsystems) ve Tosoh HLC-723 G8 HPLC sistemlerinin karşilaşilaştirilmasi (Comparison of Agilent 1100 (Chromsystems) and Tosoh HLC-723 G8 HPLC systems in thalassemia screening)

Abstract: Objective: Today, different models and trademarks of HPLC (High Performance Liquid Chromatography) equipment have been used in screening for thalassemia. However, the agreement of the results of the analyses performed by these types of equipment are unknown. In this study, the aim was to investigate the agreement between the results of the analyses of thalassemia screening performed in two sets of HPLC equipment with the Agilent 100 (Chromsystems) and the new analyzer Tosoh HLC 723 G8 trademarks. Methods: This prospective study was included in 79 (32 males and 47 females) individuals performed thalassemia screening. Statistical correlations of hemoglobin A2 (HbA2) values, analyzed in each analyzer as a single analysis from each sample were evaluated using two-way random intraclass correlation coefficient (ICC), Cohen’s kappa coefficient, correlation coefficient (r) and regression analysis. Results: As a result of the analysis, 26 of the samples (32.9%) were detected as β-thalassemia carrier, 29 (36.7%) were diagnosed as anemic and 24 (30.3%) were detected to be normal. Correlation coefficients HbA2 values were found to be as r=0.902, ICC=0.831 (p<0.0001). Regression analysis for HbA2 values were found to be as Y=0.915+0.559X (p<0.0001). However, Cohen’s kappa statistics were calculated as 1. Conclusion: According to the regression, correlation and other statistics analysis, agreement between the results HbA2 values measured in the two analyzers are found to be insufficient. However, considering the cutoff values, separation of thalassemia carriers were achieved in both systems. OZET Amac: Gunumuzde degisik marka ve modelde HPLC (High Performance Liquid Chromatog

Minor hemoglobins other than A2 in iron deficiency.

Abstract: Objective: To determine any difference in levels of minor hemoglobins, other than hemoglobin A2 (HbA2), in patients with iron deficiency. Methods: We divided ethylenediaminetetraacetic acid (EDTA)–anticoagulated blood specimens from 188 patients into 2 groups, of which 94 displayed a normal or high ferritin level and the remaining 94 had a low ferritin level. We correlated the red cell indices, hemoglobin levels, and ferritin levels with the percentage of various minor hemoglobins. The Student’s t -test was used to assess the statistical significance of the difference between the mean concentrations of minor hemoglobins in the 2 groups. Results: Only hemoglobin HbA1a had a positive correlation (0.33 in iron-deficient and 0.35 in iron-replete specimens) with serum ferritin concentration. Among the minor hemoglobins, HbA1a ( P =.008) and HbA2 ( P <.001) were significantly different between the 2 groups. Conclusion: HbA1a may be low in iron deficiency, independent of HbA2. This information may be used to predict coexistent iron deficiency in β-thalassemia traits, in which concomitant infection or inflammation leads to normal ferritin levels. * EDTA : ethylenediaminetetraacetic acid RBC : red-blood-cell CE-HPLC : ion exchange–high-performance liquid chromatography Hb : hemoglobin TIBC : total iron binding capacity MCV : mean corpusclar volume MCH : mean corpuscular hemoglobin MCHC : mean corpuscular hemoglobin concentration