Dataset Information

Hydroxyurea Treated ?-Thalassemia Children Demonstrate a Shift in Metabolism Towards Healthy Pattern.

ABSTRACT: Augmentation of fetal hemoglobin (HbF) production has been an enduring therapeutic objective in ?-thalassemia patients for which hydroxyurea (HU) has largely been the drug of choice and the most cost-effective approach. A serum metabolomics study on 40 patients with ?-thalassemia prior to and after administration of HU was done along with healthy controls. Treated patients were divided further into non-responders (NR), partial (PR) and good (GR) per their response. 25 metabolites that were altered before HU therapy at p???0.05 and fold change >2.0 in ?-thalassemia patients; started reverting towards healthy group after HU treatment. A prediction model based on another set of 70 HU treated patients showed a good separation of GR from untreated ?-thalassemia patients with an overall accuracy of 76.37%. Metabolic pathway analysis revealed that various important pathways that were disturbed in ?-thalassemia were reverted after treatment with HU and among them linoleic acid pathway was most impactfully improved in HU treated patients which is a precursor of important signaling molecules. In conclusion, this study indicates that HU is a good treatment option for ?-thalassemia patients because in addition to reducing blood transfusion burden it also ameliorates disease complications by shifting body metabolism towards normal.

SUBMITTER: Iqbal A

PROVIDER: S-EPMC6182004 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Hydroxyurea Treated β-Thalassemia Children Demonstrate a Shift in Metabolism Towards Healthy Pattern.

Iqbal Ayesha A Ansari Saqib Hussain SH Parveen Sadia S Khan Ishtiaq Ahmad IA Siddiqui Amna Jabbar AJ Musharraf Syed Ghulam SG

Scientific reports 20181011 1

Augmentation of fetal hemoglobin (HbF) production has been an enduring therapeutic objective in β-thalassemia patients for which hydroxyurea (HU) has largely been the drug of choice and the most cost-effective approach. A serum metabolomics study on 40 patients with β-thalassemia prior to and after administration of HU was done along with healthy controls. Treated patients were divided further into non-responders (NR), partial (PR) and good (GR) per their response. 25 metabolites that were alter ...[more]

PMID: 30310134

Similar Datasets

Project description:BackgroundThe frequency of the beta-thalassemia (β-thalassemia) gene in Indonesia ranges from 3 to 10%. However, in the East Java province, there is still limited information on the prevalence of β-thalassemia mutations in clinically diagnosed beta-thalassemia patients of East Java. Therefore, this study aimed to characterize β-thalassemia mutations in selected patients in the East Java province of Indonesia.MethodsThis is an analytical observational study. Diagnosis of β-thalassemia was based on clinical presentation, complete blood count (CBC), and hemoglobin (Hb) electrophoresis. Blood specimens taken from each patient in three ethylenediaminetetraacetic acid (EDTA) tubes were analyzed for CBC and Hb electrophoresis and processed for DNA extraction and subsequent polymerase chain reaction (PCR). Detection of mutations in Hemoglobin Subunit Beta (HBB) gene exons 1-3 of the β-thalassemia gene as the common mutation in Indonesia was done using PCR followed by Sanger sequencing.ResultsIn total, 33 (n = 33) participants were involved in this study with ages ranging from 5 to 17 years comprising 19 women and 14 men. Their ethnic origins were Javanese (n = 30) and Chinese (n = 3). CBC results showed that mean ± standard deviation (SD) for Hb, red blood cell (RBC), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and red cell distribution width (RDW)-CV were 81.2 ± 7.0 g/L; 3.40 ± 0.39 × 109/L; 71.05 ± 5.72 fL; 24.12 ± 2.45 pg; 33.91 ± 1.47 g/dl; 24.38 ± 6.02%, respectively. Hb electrophoresis revealed that 5 out of 33 participants had beta-thalassemia and 28 out of 33 participants had hemoglobinopathy (Hb) E/beta-thalassemia. Results of Sanger sequencing showed the following genotype variations in the samples: 12 (36.4%) with β CD26 /β IVS-I-5; 6 (18.2%) with β CD26 /β CD35; 3 (9.1%) with β CD26 /β IVS-I-2; 2 (6.1%) with β CD27/28 /β CD40; 2 (6.1%) with β IVS-I-1 /β CAP+1; and β CD26 /β IVS-I-1; β IVS-I-5 /β CAP+1; β IVS-I-5 /β CD35; β CD26 /β CD37; β CD26 /β CD15; β CD26 /β CD40; and β IVS-I-5 /β CD19 in 1 (3%) sample, respectively, and 1 (3%) had no abnormality detected in sequencing even though electrophoresis showed abnormality in the migration pattern. The β CD26 /β IVS-I-5 mutation was found in samples that were noted to have Hb E/beta-thalassemia on Hb electrophoresis.ConclusionThe underlying genetic variations are heterogeneous in thalassemia patients in East Java, where 12 variants were found. The most common variant was β CD26 /β IVS-I-5, which all accounted for Hb E/beta-thalassemia on Hb electrophoresis. Furthermore, 28 out of 33 participants had hemoglobinopathy (Hb) E/beta-thalassemia.

Dataset Information

Hydroxyurea Treated ?-Thalassemia Children Demonstrate a Shift in Metabolism Towards Healthy Pattern.

Publications

Hydroxyurea Treated β-Thalassemia Children Demonstrate a Shift in Metabolism Towards Healthy Pattern.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets