rs11886868 and rs4671393 of <i>BCL11A</i> associated with HbF level variation and modulate clinical events among sickle cell anemia patients

Chaouch, Leila; Moumni, Imen; Ouragini, Houyem; Darragi, Imen; Kalai, Miniar; Chaouachi, Dorra; Boudrigua, Imen; Hafsia, R; Abbès, Salem

doi:10.1080/10245332.2015.1107275

Cited by 17 publications

(16 citation statements)

References 18 publications

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“…In contrast, a higher proportion of an A allele of the rs4671393 (G-A) polymorphism of the BCL11A gene was detected among 122 Thai NTDT patients i.e., 28.7% in heterozygote form and 2.5% in the homozygote. This rs4671393 (G-A) polymorphism is associated with Hb F variation and clinical events in sickle anemia 27. As compared to other genes, more prevalence of the G allele of rs4895441 (A-G), the C allele of rs9399137 (T-C) and T allele of rs2297339 (C-T) of the HBS1L-MYB intergenic region were observed among our Thai NTDT patients.…”

Section: Discussionmentioning

confidence: 69%

MOLECULAR ANALYSIS OF NON-TRANSFUSION DEPENDENT THALASSEMIA ASSOCIATED WITH HEMOGLOBIN E-Β-Thalassemia DISEASE WITHOUT Α--Thalassemia

Phanrahan¹,

Yamsri²,

Teawtrakul³

et al. 2019

Mediterr J Hematol Infect Dis

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Background: The finding of many Thai Hb E-β0-thalassemia patients with non-transfusion dependent thalassemia (NTDT) phenotype without co-inheritance of α-thalassemia has prompted us to investigate the existence of other genetic modifying factors. Methods: Study was done on 146 adult Thai patients with NTDT Hb E-β0-thalassemia and a homozygous β-thalassemia patient without co-inheritance of α-thalassemia. Multiple single-nucleotide polymorphisms (SNPs) associated with γ-globin gene expression including the Gγ-XmnI of HBG2 gene, rs2297339, rs4895441, and rs9399137 of the HBS1L-MYB gene, rs4671393 in the BCL11A gene, and G176AfsX179, T334R, R238H and -154 (C-T) in the KLF1 gene were investigated using PCR-and related techniques. Results: Heterozygous and homozygous for Gg-XmnI of HBG2 gene were detected at 68.0% and 6.1%, respectively. Further DNA analysis identified the rs2297339 (C-T), rs4895441 (A-G), and rs9399137 (T-C) of HBS1L-MYB gene in 86.4%, 22.5% and 20.4%, respectively. The rs4671393 (G-A) of the BCL11A gene was found at 31.3%. For the KLF1 gene, the T334R and G176AfsX179 (+/-) were detected at 8.2% and 1.4%, respectively. Conclusion: It was found that these SNPs when analyzed in combination could explain the mild phenotypic expression of all cases. These results underline the importance of these informative SNPs on phenotypic expression of Hb E-β-thalassemia patients.

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Section: Discussionmentioning

confidence: 69%

MOLECULAR ANALYSIS OF NON-TRANSFUSION DEPENDENT THALASSEMIA ASSOCIATED WITH HEMOGLOBIN E-Β-Thalassemia DISEASE WITHOUT Α--Thalassemia

Phanrahan¹,

Yamsri²,

Teawtrakul³

et al. 2019

Mediterr J Hematol Infect Dis

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“…Copy number variation analysis of the α‐globin and β‐globin gene clusters was performed by multiplex ligation‐dependent probe amplification (MRC Holland, Amsterdam, The Netherlands). We genotyped three quantitative trait loci (QTL) associated with HbF levels in peripheral blood: the Xmn I polymorphism in the haemoglobin subunit gamma 2 ( HBG2 ) promoter (rs7482144); the erythroid‐specific enhancer of BAF chromatin remodeling complex subunit 11A ( BCL11A ; rs11886868, rs1427407, rs4671393); and the HBS1L‐MYB intergenic region (rs28384513, rs9399137) 19–21 …”

Section: Methodsmentioning

confidence: 99%

“…We genotyped three quantitative trait loci (QTL) associated with HbF levels in peripheral blood: the XmnI polymorphism in the haemoglobin subunit gamma 2 (HBG2) promoter (rs7482144); the erythroidspecific enhancer of BAF chromatin remodeling complex subunit 11A (BCL11A; rs11886868, rs1427407, rs4671393); and the HBS1L-MYB intergenic region (rs28384513, rs9399137). [19][20][21]…”

Section: Genetic Testingmentioning

confidence: 99%

Early initiation of hydroxyurea (hydroxycarbamide) using individualised, pharmacokinetics‐guided dosing can produce sustained and nearly pancellular expression of fetal haemoglobin in children with sickle cell anaemia

et al. 2021

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Hydroxyurea (hydroxycarbamide) is an effective treatment for sickle cell anaemia (SCA), but clinical responses depend primarily upon the degree of fetal haemoglobin (HbF) induction and the heterogeneity of HbF expression across erythrocytes. The number and characteristics of HbF-containing cells (F-cells) are not assessed by traditional HbF measurements. Conventional hydroxyurea dosing (e.g. fixed doses or low starting doses with stepwise escalation) produces a moderate heterocellular HbF induction, but haemolysis and clinical complications continue. Robust, pancellular HbF induction is needed to minimise or fully inhibit polymerisation of sickle haemoglobin. We treated children with hydroxyurea using an individualised, pharmacokinetics-guided regimen starting at predicted maximum tolerated dose (MTD). We observed sustained HbF induction (mean >30%) for up to 6 years, which was not dependent on genetic determinants of HbF expression. Nearly 70% of patients had ≥80% F-cells (nearpancellular), and almost half had ≥90% F-cells (pancellular). The mean HbF/F-cell content was~12 pg. Earlier age of initiation and better medication adherence were associated with high F-cell responses. In summary, early initiation of hydroxyurea using pharmacokinetics-guided starting doses at predicted MTD can achieve sustained near-pancellular or pancellular HbF expression and should be considered an achievable goal for children with SCA treated with hydroxyurea at optimal doses. Clinical trial registration number: NCT02286154 (clinicaltrials.gov).

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“…2p15-p16.1 chromosome microdeletion may lead to haploinsufficiency of BCL11A [27,28]. Some groups reported that BCL11A single-nucleotide polymorphisms (SNPs), especially rs11886868 and rs1427407, can reduce the expression of BCL11A [29,30]. Similarly, disrupt the enhancer of BCL11A gene can reduce its expression [31,32].…”

Section: Expression and Regulation Of Bcl11amentioning

confidence: 99%

BCL11A: a potential diagnostic biomarker and therapeutic target in human diseases

Yin

Xie

et al. 2019

Bioscience Reports

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Transcription factor B-cell lymphoma/leukemia 11A (BCL11A) gene encodes a zinc-finger protein that is predominantly expressed in brain and hematopoietic tissue. BCL11A functions mainly as a transcriptional repressor that is crucial in brain, hematopoietic system development, as well as fetal-to-adult hemoglobin switching. The expression of this gene is regulated by microRNAs, transcription factors and genetic variations. A number of studies have recently shown that BCL11A is involved in β-hemoglobinopathies, hematological malignancies, malignant solid tumors, 2p15-p16.1 microdeletion syndrome, and Type II diabetes. It has been suggested that BCL11A may be a potential prognostic biomarker and therapeutic target for some diseases. In this review, we summarize the current research state of BCL11A, including its biochemistry, expression, regulation, function, and its possible clinical application in human diseases.

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rs11886868 and rs4671393 of BCL11A associated with HbF level variation and modulate clinical events among sickle cell anemia patients

Cited by 17 publications

References 18 publications

MOLECULAR ANALYSIS OF NON-TRANSFUSION DEPENDENT THALASSEMIA ASSOCIATED WITH HEMOGLOBIN E-Β-Thalassemia DISEASE WITHOUT Α--Thalassemia

MOLECULAR ANALYSIS OF NON-TRANSFUSION DEPENDENT THALASSEMIA ASSOCIATED WITH HEMOGLOBIN E-Β-Thalassemia DISEASE WITHOUT Α--Thalassemia

Early initiation of hydroxyurea (hydroxycarbamide) using individualised, pharmacokinetics‐guided dosing can produce sustained and nearly pancellular expression of fetal haemoglobin in children with sickle cell anaemia

BCL11A: a potential diagnostic biomarker and therapeutic target in human diseases

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