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Association between BCL11A, HSB1L-MYB, and XmnI γG-158 (C/T) gene polymorphism and hemoglobin F level in Egyptian sickle cell disease patients.

BCL11A、HSB1L-MYB和XmnI γ g-158 (C/T) 基因多态性与埃及镰状细胞病患者血红蛋白F水平的相关性。

  • 影响因子:1.94
  • DOI:10.1007/s00277-020-04187-z
  • 作者列表:"El-Ghamrawy M","Yassa ME","Tousson AMS","El-Hady MA","Mikhaeil E","Mohamed NB","Khorshied MM
  • 发表时间:2020-10-01
Abstract

:Sickle cell disease (SCD) is a monogenic disease characterized by multisystem morbidity and highly variable clinical course. Inter-individual variability in hemoglobin F (HbF) levels is one of the main modifiers that account for the clinical heterogeneity in SCD. HbF levels are affected by, among other factors, single nucleotide polymorphisms (SNPs) at the BCL11A gene and the HBS1L-MYB intergenic region and Xmn1 gene. Our aim was to investigate HbF-enhancer haplotypes at these loci to obtain a first overview of the genetic situation of SCD patients in Egypt and its impact on the severity of the disease. The study included 100 SCD patients and 100 matched controls. Genotyping of BCL11A (rs1886868 C/T), HBS1L-MYB (rs9389268 A/G) and Xmn1 γG158 (rs7842144 C/T) SNPs showed no statistically significant difference between SCD patients and controls except for the hetero-mutant genotypes of BCL11A which was significantly higher in SCD patients compared with controls. Baseline HbF levels were significantly higher in those with co-inheritance of polymorphic genotypes of BCL11A + HSB1L-MYB and BCL11A + Xmn1. Steady-state HbF levels, used as an indicator of disease severity, were significantly higher in SCD-Sβ patients having the polymorphic genotypes of HSB1L-MYB. Fold change of HbF in both patient groups did not differ between those harboring the wild and the polymorphic genotypes of the studied SNPs. In conclusion, BCL11A, HSB1L, and Xmn1 genetic polymorphisms had no positive impact on baseline HbF levels solely but had if coexisted. Discovery of the molecular mechanisms controlling HbF production could provide a more effective strategy for HbF induction.

摘要

: 镰状细胞病 (SCD) 是一种单基因疾病,其特征在于多系统发病率和高度可变的临床病程。血红蛋白F (HbF) 水平的个体间变异性是导致SCD临床异质性的主要调节剂之一。除其他因素外,HbF水平受BCL11A基因和HBS1L-MYB基因间区和Xmn1基因的单核苷酸多态性 (snp) 的影响。我们的目的是调查这些位点的HbF增强子单倍型,以获得埃及SCD患者遗传情况及其对疾病严重程度的影响的第一概述。该研究包括100名SCD患者和100名匹配的对照。BCL11A (rs1886868 C/T) 、HBS1L-MYB (rs9389268a/G) 和Xmn1 γ g158 (rs7842144 C/T) SNPs的基因分型在SCD患者和对照之间没有统计学显著差异,除了BCL11A的异突变基因型在SCD患者中显著高于对照。BCL11A   +   HSB1L-MYB和BCL11A   +   xmn1多态性基因型共遗传的患者基线HbF水平显著较高。作为疾病严重程度指标的稳态HbF水平在具有HSB1L-MYB的多态性基因型的SCD-s β 患者中显著更高。两个患者组中HbF的倍数变化在具有野生型和所研究的snp的多态性基因型的患者之间没有差异。总之,BCL11A、HSB1L和Xmn1基因多态性单独对基线HbF水平没有积极影响,但如果共存的话。发现控制HbF产生的分子机制可以为HbF诱导提供更有效的策略。

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影响因子:1.74
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血红蛋白病方向

由于血红蛋白分子结构异常(异常血红蛋白病),或珠蛋白肽链合成速率异常(珠蛋白生成障碍性贫血,又称海洋性贫血)所引起的一组遗传性血液病。

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