Genetic Background of β Thalassemia Modifier: Recent Update

Rujito, Lantip; Sasongko, Teguh Haryo

doi:10.14710/jbtr.v4i1.2541

Cited by 5 publications

(4 citation statements)

References 75 publications

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“…The primary modifier is a mutation in the beta genes, whereas the subsequent modification is the involvement of hemoglobin F coding genes and co-inheritance with alpha genes mutations. (11) Repeated transfusion has been known as the cause of redox reaction disturbance due to iron overload. GSTM1 and GSTT1 genes are among the possible factors that play a role in the clinical modification process of thalassemia patients.…”

Section: Resultsmentioning

confidence: 99%

Glutathione S transferase and catalase gene polymorphisms did not tend to influence the severity of hemoglobin E/β-thalassemia

et al. 2020

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Background Thalassemia, a monogenic genetic disease of red blood cells, is spread widely throughout the world. Glutathione S transferase (GST) enzymes have an antioxidant role in detoxification processes of toxic substances This study aimed to determine the role of the genetic modifier genes GSTT1 and GSTM1, and the catalase (CAT) gene in clinical degrees of hemoglobin (Hb)E/β thalassemia. Methods Sixty HbE/β Thalassemia patients were examined to determine their clinical pictures. Clinical score was based on age when thalassemia symptoms appeared, time of diagnosis, time of first blood transfusion, pre-transfusion hemoglobin concentration, frequency of transfusions, and enlargement of spleen. Ferritin concentration was also obtained from medical records. Gene polymorphisms of GSTT1, GSTM1, and CAT were measured using PCR and PCR-RFLP methods. Clinical scores were categorized into mild (0-3.5), moderate (4-7), and severe (7.5-10) degrees, while ferritin level was expressed in mg/dL. One way Anova was used to analyze the data. Results The clinical appearance showed that severe, moderate, and mild degrees accounted for 42%, 45%, and 13%, respectively. The majority had a high ferritin level of more than 5000 mg/dL (67%). GSTT1 null, GSTM1 null, and CAT minor allele genotypes were 21.7%, 33.3%, and 12.1%, respectively. GSTT1, GSTM1, and CAT genotypes had no impact on the severity of thalassemia patients (p=0.091, p=0.082, and p=0.141, respectively). Conclusion GSTT1, GSTM1, CAT gene polymorphisms tend to be a minor aspect of severity of clinical outcome for HbE/â thalassemia patients and should be not considered a routine laboratory check.

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Section: Resultsmentioning

confidence: 99%

Glutathione S transferase and catalase gene polymorphisms did not tend to influence the severity of hemoglobin E/β-thalassemia

et al. 2020

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“…Two important secondary modifiers -co-inheritance of α-thalassemia and variants associated with increased HbF synthesis -have emerged, but they do not explain all clinical heterogeneity [36]. The genes involved are HBA, HBG, BCL11A, HBS1L-MYB and other cofactor genes regulating erythropoiesis [37]. Recent studies revealed that other genetic modifiers, not affecting globin imbalance directly, might moderate secondary manifestations of heterozygous β-thalassemia and response to therapies.…”

Section: Discussionmentioning

confidence: 99%

“…339-344). Thus, in the era of molecular medicine, β-thalassemia carriers have a unique opportunity for additional genetic testing and secondary prevention strategy [37,39,41].…”

Section: Discussionmentioning

confidence: 99%

The Relevance of β-Thalassemia Heterozygosity in Pediatric Clinical Practice: Croatian Experience

Dordevic,

Ugrin,

Mrakovcic Sutic

et al. 2024

Preprint

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Thalassemia syndromes are common monogenic disorders that represent a significant global health issue. No systematic epidemiological and molecular investigations on thalassemias in Croatian population have been reported to date. This prospective study included 70 children with a presumptive diagnosis of thalassemia, and their 42 first-degree relatives. Molecular characterization was performed using direct sequencing and gap-PCR methods. We identified 46 (30 children and 16 first-degree relatives) β-thalassemia heterozygous carriers from 24 unrelated families, carrying eight different mutations and one hemoglobin variant. Five variants account for approximately 85% of all affected β-globin alleles: Hb Lepore-Boston-Washington (32,6%), HBB: c.93-21G&gt;A (19,6%), HBB:c.315+1G&gt;A (13,1%), HBB:c.92+1G&gt;A (10,9%), and HBB:c.92+6T&gt;C variant (8,7%). A need for more detailed genetic profiling of β-thalassemia carriers is emphasized since genetic modifiers can significantly impact their phenotype. Our study provides important new insights into the relevance of β-thalassemia heterozygosity in the pediatric clinical practice.

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“…This would highly propose the coinheritance of disease modifiers such as single nucleotide polymorphism in the three major quantitative trait loci (QTLs) to induce Hb F synthesis and/or inheritance of α-thalassemia to modify the unbalance between α: β globin chains and subsequently less ineffective erythropoiesis. 33 …”

Section: Discussionmentioning

confidence: 99%

Molecular Characterization and Disease-Related Morbidities of β-Thalassemia Patients from the Northeastern Part of Iraq

Amin¹,

Jalal

Ali

et al. 2020

IJGM

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Background β-thalassemia is a significant problem in the northeastern part of Iraq, and has imposed a huge burden on the health authorities. Objective To identify the molecular characterization and morbidity prevalence in transfusion-dependent thalassemia (TDT) and non-transfusion dependent thalassemia (NTDT) phenotypes in northeastern Iraq. Patients and Methods This is a cross-sectional study conducted on 242 β-thalassemia patients from 162 families. Reverse hybridization technique and direct gene sequencing were used to characterize β-thalassemia mutations, and medical records of the patients were reviewed with a well-designed questionnaire. Results A total of 22 β-globin mutations arranged in 53 different genotypes were identified: IVS-II-1 (G> A) (35.7%), followed by IVS-I-6 (T> C) (18.0%), and codon 8/9 (+G) (8.5%) were the most frequent. Among disease-related morbidities, bone disease amounted to (66.9%), followed by endocrinopathies (32.2%), hepatobiliary complications (28.9%), and pulmonary hypertension (9.9%), whereas thrombosis, extramedullary hemopoiesis, and leg ulcers were less frequent. Conclusion The overall complications rate was 78.9%, with a growing probability of complications with advanced age, with evidently higher rates in patients with β 0 β 0 and β 0 β + genotypes that explain the role of underlying genetic defects in the pathophysiology of disease complications.

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Genetic Background of β Thalassemia Modifier: Recent Update

Cited by 5 publications

References 75 publications

Glutathione S transferase and catalase gene polymorphisms did not tend to influence the severity of hemoglobin E/β-thalassemia

Glutathione S transferase and catalase gene polymorphisms did not tend to influence the severity of hemoglobin E/β-thalassemia

The Relevance of β-Thalassemia Heterozygosity in Pediatric Clinical Practice: Croatian Experience

<p>Molecular Characterization and Disease-Related Morbidities of β-Thalassemia Patients from the Northeastern Part of Iraq</p>

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