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Predictive SNPs for β⁰-thalassemia/HbE disease severity.

ABSTRACT: β-Thalassemia/HbE disease has a wide spectrum of clinical phenotypes ranging from asymptomatic to dependent on regular blood transfusions. Ability to predict disease severity is helpful for clinical management and treatment decision making. A thalassemia severity score has been developed from Mediterranean β-thalassemia patients. However, different ethnic groups may have different allele frequency and linkage disequilibrium structures. Here, Thai β⁰-thalassemia/HbE disease genome-wild association studies (GWAS) data of 487 patients were analyzed by SNP interaction prioritization algorithm, interacting Loci (iLoci), to find predictive SNPs for disease severity. Three SNPs from two SNP interaction pairs associated with disease severity were identifies. The three-SNP disease severity risk score composed of rs766432 in BCL11A, rs9399137 in HBS1L-MYB and rs72872548 in HBE1 showed more than 85% specificity and 75% accuracy. The three-SNP predictive score was then validated in two independent cohorts of Thai and Malaysian β⁰-thalassemia/HbE patients with comparable specificity and accuracy. The SNP risk score could be used for prediction of clinical severity for Southeast Asia β⁰-thalassemia/HbE population.

SUBMITTER: Munkongdee T

PROVIDER: S-EPMC8121782 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Predictive SNPs for β<sup>0</sup>-thalassemia/HbE disease severity.

Munkongdee Thongperm T Tongsima Sissades S Ngamphiw Chumpol C Wangkumhang Pongsakorn P Peerapittayamongkol Chayanon C Hashim Hafizah Binti HB Fucharoen Suthat S Svasti Saovaros S

Scientific reports 20210514 1

β-Thalassemia/HbE disease has a wide spectrum of clinical phenotypes ranging from asymptomatic to dependent on regular blood transfusions. Ability to predict disease severity is helpful for clinical management and treatment decision making. A thalassemia severity score has been developed from Mediterranean β-thalassemia patients. However, different ethnic groups may have different allele frequency and linkage disequilibrium structures. Here, Thai β<sup>0</sup>-thalassemia/HbE disease genome-wild ...[more]

PMID: 33990643

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Project description:BackgroundLow HbF expression in HbE-β+-thalassemia may lead to misdiagnosis of HbE heterozygosity. We aimed to characterize the β- and α-globin genes and the modifying factors related to HbF expression in patients with an Hb phenotype similar to that of HbE heterozygotes. Furthermore, screening tools for differentiating HbE-β+-thalassemia from HbE heterozygotes have been investigated.Participants and methodsA total of 2133 participants with HbE and HbA with varying HbF levels were recruited. Polymerase chain reaction-based DNA analysis and sequencing were performed to characterize β- and α-globin genes. DNA polymorphism at position -158 nt 5' to Gγ-globin was performed by XmnI restriction digestion. Receiver operating characteristic (ROC) curves were constructed using the area under the curve (AUC). Cutoff values of HbA2, HbE, and HbF levels for the differentiation of HbE-β+-thalassemia from HbE heterozygotes were determined.ResultsFive β+-thalassemia mutations trans to βE-gene (β-87(C>A), β-31(A>G), β-28(A>G), β19(A>G), and β126(T>G)) were identified in 79 patients. Among these, 54 presented with low HbF levels, and 25 presented with high HbF levels. ROC curve analysis revealed an excellent AUC of 1.000 (95% confidence interval:1.000-1.000) for HbE levels, and a cut-off point of ≥35.0% had 100.0% sensitivity, specificity, and Youden's index for differentiating HbE-β+-thalassemia from HbE heterozygotes. The proportion of α-thalassemia mutations was 46.3 and 8.0% among HbE-β+-thalassemia patients with low and high HbF levels, respectively. Two rare α-thalassemia mutations (Cap +14(C>G) and initiation codon (ATG>-TG)) of α2-globin genes were identified. The genotype and allele of the polymorphism at -158 nt 5' to Gγ-globin was found to be negatively associated with HbF expression.ConclusionsHbE-β+-thalassemia cannot be disregarded until appropriate DNA analysis is performed, and the detection of α-thalassemia mutations should always be performed under these conditions. An HbE level ≥35.0% may indicate screening of samples for DNA analysis for HbE-β+-thalassemia diagnosis.

Dataset Information

Predictive SNPs for β⁰-thalassemia/HbE disease severity.

Publications

Predictive SNPs for β<sup>0</sup>-thalassemia/HbE disease severity.

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Predictive SNPs for β0-thalassemia/HbE disease severity.

Publications

Predictive SNPs for β<sup>0</sup>-thalassemia/HbE disease severity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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Predictive SNPs for β⁰-thalassemia/HbE disease severity.