镰状细胞病(SCD)在临床上表现为多种并发症。Stroke,缺血性和出血性,以及无声的白质变化,发生在相对较高的患病率。了解中风最可能发生的原因和原因对于有效预防和治疗SCD患者至关重要。基因研究,包括全基因组和外显子组关联研究(GWAS和EWAS),已经发现了几个关键的修饰物,这些修饰物通过包括血红蛋白F(HbF)调节在内的机制与SCD中的卒中/卒中风险增加相关,炎症,细胞粘附,内皮破裂,和溶血。我们对迄今为止最清楚地证明了关联的修饰语进行了综述。需要更多的研究来验证其他潜在的多态性并识别新的多态性。在临床护理中纳入以基因为中心的筛查可以提供更有针对性的途径,更有效,在这一人群中预防中风的毒性较低。本综述的数据将用于告知国际血红蛋白病研究网络(INHERENT)联盟进行的初始GWAS。
Sickle cell disease (SCD) clinically manifests itself with a myriad of complications. Stroke, both ischemic and hemorrhagic, as well as silent white matter changes, occurs at a relatively high prevalence. Understanding why and in whom stroke is most likely to occur is critical to the effective prevention and treatment of individuals with SCD. Genetic studies, including genome- and exome-wide association studies (GWAS and EWAS), have found several key modifiers associated with increased stroke/stroke risk in SCD via mechanisms including Hemoglobin F (HbF) modulation, inflammation, cellular adhesion, endothelial disruption, and hemolysis. We present a
review on the modifiers that have most clearly demonstrated an association to date. More studies are needed to validate other potential polymorphisms and identify new ones. Incorporating gene-focused screenings in clinical care could provide avenues for more targeted, more effective, and less toxic prevention of stroke in this population. The data from this
review will be used to inform the initial GWAS performed by the International Hemoglobinopathy Research Network (INHERENT) consortium.