Department of Pediatrics, Division of Pediatric Hematology-Oncology, Charles-Bruneau Cancer Center, CHU Sainte-Justine, Université de Montréal; Montreal Heart Institute, 5000 Belanger Street, Montreal, Quebec H1T 1C8, Canada.
Department of Medicine, Duke University Medical Center, Durham, NC 27707, USA; Duke Molecular Physiology Institute, Duke University Medical Center, 300 North Duke Street, Durham, NC 27701, USA.
Hematol Oncol Clin North Am. 2022 Dec;36(6):1097-1124. doi: 10.1016/j.hoc.2022.06.006.
Sickle cell disease (SCD) is characterized by tremendous phenotypic heterogeneity across patients, but this clinical variability is poorly understood, thus motivating the search for genetic modifiers. The early identification of genetic variants that control fetal hemoglobin levels-a strong modifier of severity in SCD-served as a powerful example in support of these genetic experiments. Although there have been successful discoveries (eg, UGT1A, APOL1), many of the reported genetic associations remain controversial. The emergence of large-scale SCD cohorts and their integration into genetic and other omic-type research programs should bring SCD patients closer to the promises of precision medicine.
镰状细胞病（SCD）的患者之间表现出巨大的表型异质性，但这种临床变异性尚不清楚，因此需要寻找遗传修饰因子。早期确定控制胎儿血红蛋白水平的遗传变异体（SCD 严重程度的一个重要修饰因子），为这些遗传实验提供了有力的支持。尽管已经有了成功的发现（如 UGT1A、APOL1），但许多报道的遗传关联仍然存在争议。大规模 SCD 队列的出现及其纳入遗传和其他组学研究计划中，应该使 SCD 患者更接近精准医学的承诺。
