Qadah Talal, Noorwali Abdulwahab, Alzahrani Fatma, Banjar Alaa, Filimban Najlaa, Felimban Raed
Regenerative Medicine Unit, King Fahad Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, P.O. Box: 80324, Jeddah, 21589 Saudi Arabia.
Indian J Hematol Blood Transfus. 2020 Oct;36(4):705-710. doi: 10.1007/s12288-020-01270-3. Epub 2020 Mar 3.
Sickle Cell Anemia (SCA) is one of the most common monogenic disorders worldwide. Molecular modifiers of clinical symptoms play an essential role in the amelioration of the effects of the disease. Single Nucleotide Polymorphisms (SNPs) of the BCL11A gene and within the HBS1L-MYB intergenic region, which are located outside the β-globin locus on chromosome 11, are considered to be genetic modifiers that are associated with elevated levels of foetal haemoglobin HbF, and thus they reduce the clinical impact of sickle haemoglobin, HbS. The work reported here aimed to detect the most common SNPs of BCL11A and HBS1L-MYB related to HbF in SCA patients and to estimate the frequency of occurrence of these genotypes. A total of 132 SCA patients whose condition was stable were recruited from Jeddah city, Saudi Arabia. SNPs at site locus rs4671393 on BCL11A, and at loci rs28384513 and rs9399137 on HBS1L-MYB were identified using TaqMan genotyping assay. Haematological parameters were analysed based on complete blood count and haemoglobin separation using the capillary electrophoresis technique. Highly significant differences in the diagnostic haematological parameters, including all blood-cell types and HbF, were observed between the study cohort and control groups. We also found that BCL11A rs4671393 genotypes of GG and AG were more likely to show increases in HbF levels than other genotypes. In addition, a strong relationship was found between HBS1L-MYB rs9399137 and rs28384513 genotypes in the cohort, whereas no significant association was observed between BCL11A rs4671393 variant and other variants. Our study highlights the importance of investigating genetic determinants that play roles in the amelioration of the severity of clinical symptoms and complications of SCA.
镰状细胞贫血（SCA）是全球最常见的单基因疾病之一。临床症状的分子修饰因子在改善该疾病的影响方面起着至关重要的作用。位于11号染色体β-珠蛋白基因座之外的BCL11A基因以及HBS1L-MYB基因间区域内的单核苷酸多态性（SNP）被认为是与胎儿血红蛋白HbF水平升高相关的遗传修饰因子，因此它们可减轻镰状血红蛋白HbS的临床影响。本文报道的研究旨在检测SCA患者中与HbF相关的BCL11A和HBS1L-MYB最常见SNP，并估计这些基因型的发生频率。从沙特阿拉伯吉达市招募了132名病情稳定的SCA患者。使用TaqMan基因分型检测法鉴定了BCL11A基因座rs4671393位点以及HBS1L-MYB基因座rs28384513和rs9399137位点的SNP。基于全血细胞计数和使用毛细管电泳技术进行血红蛋白分离来分析血液学参数。在研究队列和对照组之间观察到诊断血液学参数（包括所有血细胞类型和HbF）存在高度显著差异。我们还发现，与其他基因型相比，BCL11A rs4671393基因型GG和AG更有可能显示HbF水平升高。此外，在该队列中发现HBS1L-MYB rs9399137和rs28384513基因型之间存在强相关性，而未观察到BCL11A rs4671393变体与其他变体之间存在显著关联。我们的研究强调了调查在改善SCA临床症状严重程度和并发症中起作用的遗传决定因素的重要性。
