Genetic polymorphisms of HbE/beta thalassemia related to clinical presentation: implications for clinical diversity

Azman, Nurul Fatihah; Abdullah, Wan Zaidah; Hanafi, Sarifah; Diana, Rachel A.; Bahar, Rosnah; Johan, Muhammad Farid; Zilfalil, Bin Alwi; Hassan, Rosline

doi:10.1007/s00277-020-03927-5

Cited by 6 publications

(4 citation statements)

References 14 publications

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“…β-thalassemia/Hb E disease showed diverse disease phenotypes ranging from mild to severely affected patients ( 6 , 21 ). The variation in disease severity in β-thalassemia patients could be explained by β-thalassemia mutations ( 10 ), α-thalassemia interactions ( 35 , 36 ), and genetic determinants of Hb F production ( 15 , 17 , 18 , 37 , 38 ), and other factors related to the pathophysiology of β-thalassemia ( 39-41 ). Several genetic modifiers associated with disease severity and fetal hemoglobin levels in β-thalassemia/Hb E patients have been well studied in the Thai population ( 10 , 17 , 18 ).…”

Section: Discussionmentioning

confidence: 99%

Genetic predictions of life expectancy in southern Thai patients with β0‑thalassemia/Hb E

et al. 2022

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The types of β-thalassemia mutations, α-thalassemia interactions, and Hb F-associated SNPs have been described in association with variable disease phenotypes. This study aimed to determine the updated spectrum of β-thalassemia mutations and evaluate the contribution of primary and secondary genetic modifiers and SNPs to disease severity, age at onset, and predicted life expectancy in southern Thai β-thalassemia patients. A total of 181 β-thalassemia patients were enrolled and 135 β 0 -thalassemia/Hb E patients without α-thalassemia interactions were divided into three categories according to disease severity, age at onset, and predicted life expectancy. A total of 16 β-thalassemia mutations were identified in this study, and the three most common β-thalassemia mutations accounted for 61.4% of all mutations. It was also found that the Xmn I polymorphism and rs2071348 were associated with age at onset and the predicted life expectancy. More than 82% of β 0 -thalassemia/Hb E patients with CC genotype ( Xmn I) were 3 years old or younger at onset. Additionally, >90% of the higher predicted life expectancy in β 0 -thalassemia/Hb E patients had the T allele of Xmn I. Therefore, genetic prediction for age at onset and life expectancy is beneficial and practical during prenatal diagnosis or newborn screening for better genetic counseling and optimal management.

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Section: Discussionmentioning

confidence: 99%

Genetic predictions of life expectancy in southern Thai patients with β0‑thalassemia/Hb E

et al. 2022

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“…The PLINK software was used to filter irrelevant SNPs, including those on the X and Y chromosomes and the mitochondrial genome. During PLINK analysis, genotyping call rate (0.05) was used as the SNP filtering parameter to remove missing genotypes of the SNPs [ 28 ]. Male and female subjects were analyzed in stratification.…”

Section: Methodsmentioning

confidence: 99%

Variation in Genotype and DNA Methylation Patterns Based on Alcohol Use and CVD in the Korean Genome and Epidemiology Study (KoGES)

Jung

Ahn

Chang

et al. 2022

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Alcohol consumption can increase the risk of chronic diseases, such as myocardial infarction, coronary artery disease, hyperlipidemia, and hypertension. We aimed to assess the association between genotype, DNA methylation patterns, alcohol consumption, and chronic diseases in Korean population. We analyzed 8840 subjects for genotypes and 446 for DNA methylation among the 9351 subjects from the Korean Genome and Epidemiology Study (KoGES). We further divided both groups into two sub-groups according to the presence/absence of chronic diseases. We selected genes whose methylation varied significantly with alcohol consumption, and visualized genotype and DNA methylation patterns specific to each group. Genome-wide association study (GWAS) revealed single nucleotide polymorphisms (SNPs) rs2074356 and rs11066280 in HECT domain E3 ubiquitin protein ligase 4 (HECTD4) to be significantly associated with alcohol consumption in both the presence. The rs12229654 genotype also displayed significantly different patterns with alcohol consumption. Furthermore, we retrieved differentially methylated regions (DMRs) from four groups based on sex and chronic diseases and compared them by drinking status. In genotype analysis, cardiovascular diseases (CVDs) showed a higher proportion in drinker than in non-drinker, but not in DMR analysis. Additionally, we analyzed the enriched Gene Ontology terms and Kyoto Gene and Genome Encyclopedia (KEGG) pathways and visualized the network, heatmap, and upset plot. We show that the pattern of DNA methylation associated with CVD is strongly influenced by alcoholism. Overall, this study identified genetic and epigenetic variants influenced by alcohol consumption and chronic diseases.

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“…Since 2005, DFO and oral DFP have become freely available and accessible to patients, while DFX had been more accessible in 2012 (14). In 2006, the Malaysian government had set aside a total of RM25 million per year for the provision of free treatment to all thalassemia patients.…”

Section: Introductionmentioning

confidence: 99%

Barriers to adherence to iron chelation therapy among adolescent with transfusion dependent thalassemia

et al. 2022

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Study backgroundThalassemia is the commonest genetic blood disorder in Malaysia which requires life-long blood transfusions. From a total of 7,984 thalassemia patients in Malaysia, adolescent age group account for the highest number of patients (2,680 patients, 33.57%). In developed countries, the average rate of adherence to long-term treatment among children and adolescents is only 58%. Sub-optimal adherence to iron chelation therapy may impact the outcome and quality of life in these patients. Thus, assessing adherence level and identification of risk factors for non-adherence is essential in optimizing management.ObjectivesTo determine the association between mean serum ferritin level with self-reported level of adherence to iron chelation therapy in transfusion dependent thalassemia (TDT) adolescents in Hospital Tengku Ampuan Afzan (HTAA), Kuantan and Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Cheras; to determine the association between socio-demographic factors and patients’ knowledge on thalassemia and iron chelation therapy with the level of adherence.Materials and methodsThis was a cross-sectional study conducted between 1st March 2019 and 31st March 2020. Data was collected through face-to-face interview by a single interviewer during the thalassemia clinic follow up, with content validated questionnaires. The questionnaires comprised four sections which included socio-demographic data, medication adherence questionnaire, knowledge of disease, and clinical characteristics of the participants.ResultsA total of 70 participants were recruited. Results showed that only 51.4% of participants had good adherence to iron chelation therapy. There was a significant association between monthly household incomes of the family with the level of adherence to iron chelation (p-value 0.006). There was also an association between the mean serum ferritin levels with total Adherence Starts with Knowledge (ASK-12) score (p-value 0.001). However, there was no association between knowledge on thalassemia with the level of adherence.ConclusionAdherence to iron chelation was generally unsatisfactory amongst adolescents with TDT as only 51.4% had good adherence. Low monthly household income of the family may affect adherence to iron chelation therapy in TDT patients. As adherence remains to be an issue amongst adolescent thalassemia patients, management should include regular and objective assessments to address this problem so as to optimize patient outcome.

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Genetic polymorphisms of HbE/beta thalassemia related to clinical presentation: implications for clinical diversity

Cited by 6 publications

References 14 publications

Genetic predictions of life expectancy in southern Thai patients with β0‑thalassemia/Hb E

Genetic predictions of life expectancy in southern Thai patients with β0‑thalassemia/Hb E

Variation in Genotype and DNA Methylation Patterns Based on Alcohol Use and CVD in the Korean Genome and Epidemiology Study (KoGES)

Barriers to adherence to iron chelation therapy among adolescent with transfusion dependent thalassemia

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