Fetal-haemoglobin enhancing genotype at BCL11A reduces HbA(2) levels in patients with sickle cell anaemia.
Fetal-haemoglobin enhancing genotype at BCL11A reduces HbA(2) levels in patients with sickle cell anaemia.
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DOI：
10.1002/jha2.186
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发表时间：
2021-08
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了解遗传因素与镰状细胞病中血红蛋白表达和病理过程的相互作用对于药物和基因治疗干预非常重要。在我们对尼日利亚患者的新生研究队列中，我们发现三个主要的疾病修饰因素，HbF水平，α地中海贫血缺失和BCL 11 A基因型，具有预期的有益血液学效应。一种关键的BCL 11 A变体，在改善HbF水平（5.7%-9.0%）的同时，也导致HbA 2小幅但显著降低。我们的结论是，在一般情况下，提高HbF的干预措施可能会降低患者红系细胞中的HbA 2，这种治疗策略可能会受益于通过独立的机制平行刺激HbA 2。
Understanding the interplay of genetic factors with haemoglobin expression and pathological processes in sickle cell disease is important for pharmacological and gene‐therapeutic interventions. In our nascent study cohort of Nigerian patients, we found that three major disease‐modifying factors, HbF levels, α‐thalassaemia deletion and BCL11A genotype, had expected beneficial haematological effects. A key BCL11A variant, while improving HbF levels (5.7%–9.0%), also led to a small, but significant decrease in HbA2. We conclude that in general, interventions boosting HbF are likely to reduce HbA2 in patients’ erythroid cells and that such therapeutic strategies might benefit from a parallel stimulation of HbA2 through independent mechanisms.