Dataset Information

Haemoglobin switching modulator SNPs rs5006884 is associated with increased HbA₂ in β-thalassaemia carriers.

ABSTRACT:

Introduction

Haemoglobin A₂ (HbA₂), the tetramer of α- and δ-globin chains, is used as a diagnostic biomarker for β-thalassaemia carriers. The HbA₂ levels are regulated by the presence of HPFH, δ-thalassaemia, HbA_1/2 gene triplication, and variants of KLF1, β-globin gene, and HbF regulating QTLs. Saudi Arabia has a high incidence of borderline HbA₂ levels, thereby making it difficult to classify the haemoglobinopathies. This study aims to investigate the association of known HbF enhancer QTL gene SNPs with HbA₂ levels.

Material and methods

14 Specific SNPs in BCL11A, HMIP, OR51B6, HBBP1, and HBG2 loci were genotyped in 164 Saudi β-thalassaemia carriers by TaqMan assay to validate their role as regulators of HbA₂ levels. HbA2 levels were determined using the Variant II β-Thalassemia Short Program Recorder kit. The non-random association of these SNPs was tested using HaploView software. Protein interaction was assessed using 3D structure modelling for OR51B6 (rs5006884), comparative energy minimisation, and root-mean-square deviation (RMSD) prediction.

Results

Elevated HbA₂ levels were associated with SNPs in HBBP1, OR51B6, and TCT haplotype from HBG2 promoter region. The bioinformatics modelling and prediction revealed that the exonic rs5006884 had RMSD value deviations and significantly varied binding energy minimisation. α-globin variations were found in 57.92% of individuals but were not associated with elevated HbA₂.

Conclusions

The haemoglobin switching modulators rs2071348, rs7482144, and rs5006884 are involved in regulation of HbA₂ level with rs5006884 influencing the tetramer formation. Screening for haemoglobinopathies should take these SNPs into consideration, specifically in borderline HbA₂ cases. Assiduous analysis of rs5006884 as HbA₂ modulator for amelioration of disease severity is recommended.

SUBMITTER: Cyrus C

PROVIDER: S-EPMC8314410 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Tests for haemoglobinopathy carrier status are the commonest genetic screening tests undertaken internationally. Carrier screening for β-thalassaemia is not coordinated in Victoria, Australia, and is instead incorporated into routine practice where most women are screened antenatally, through a full blood examination (FBE). Little is known about how women are screened for β-thalassaemia in Australia as well as their attitudes towards the screening process. This study was conducted to explore carriers' and carrier couples' experiences of and attitudes towards β-thalassaemia screening in Australia. Semi-structured interviews with 26 recently pregnant female carriers and ten carrier couples of β-thalassaemia were carried out. Interviews were analysed using inductive content analysis. Unexpectedly, more than half of the women had been made aware of their carrier status prior to pregnancy, with FBEs carried out for numerous reasons other than thalassaemia screening. Most women did not recall being told about thalassaemia before notification of their carrier status and therefore did not make a decision about being screened. They were generally accepting for doctors to decide about testing; however, would have preferred to have been made aware of the screening test. Women also reported receiving insufficient information after being notified of their carrier status, leading to misconceptions and confusion. This genetic screening process, incorporated into routine care whereby informed decisions were not being made by patients, was apparently acceptable overall. Based on the results of this study, we make the following recommendations: (1) individuals should be made aware that they are being tested for thalassaemia at least before a specific thalassaemia diagnostic test is performed; (2) current understanding by known carriers of thalassaemia should be assessed and any misconceptions corrected; (3) written information should be provided to carriers; (4) referral of carrier couples to specialists in thalassaemia and genetics is strongly recommended; (5) the term 'carrier of β-thalassaemia' should be used rather than 'thalassaemia minor'.

Dataset Information

Haemoglobin switching modulator SNPs rs5006884 is associated with increased HbA₂ in β-thalassaemia carriers.

Introduction

Material and methods

Results

Conclusions

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Haemoglobin switching modulator SNPs rs5006884 is associated with increased HbA2 in β-thalassaemia carriers.

Introduction

Material and methods

Results

Conclusions

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Haemoglobin switching modulator SNPs rs5006884 is associated with increased HbA₂ in β-thalassaemia carriers.