Sickle Cell Disease in the Post Genomic Era: A Monogenic Disease with a Polygenic Phenotype
Sickle Cell Disease in the Post Genomic Era: A Monogenic Disease with a Polygenic Phenotype
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DOI：
10.4137/gei.s2626
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发表时间：
2009-07
期刊：
影响因子：
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通讯作者：
Adel Driss;Kwaku Asare;J. Hibbert;Beatrice E. Gee;Tom Adamkiewicz;Jonathan K. Stiles
中科院分区：
文献类型：
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作者：
Adel Driss;Kwaku Asare;J. Hibbert;Beatrice E. Gee;Tom Adamkiewicz;Jonathan K. Stiles
镰状细胞病（SCD）的分子基础被发现已经超过半个世纪，但该疾病表型异质性的原因仍不清楚。这种异质性表现为不同的临床结局，如卒中、血管闭塞发作、急性胸部综合征、缺血性坏死、腿部溃疡、阴茎异常勃起和视网膜病变。这些结果不能单独用β-珠蛋白基因的单一突变来解释，但可能归因于遗传修饰剂和环境影响。后人类基因组测序时代的最新进展为SCD中新型遗传修饰剂的鉴定打开了大门。研究表明，SCD的表型似乎是由参与炎症、细胞-细胞相互作用和氧化损伤和一氧化氮生物学调节剂的基因多态性调节的。发现与不同表型有关的基因将有助于理解疾病的病理生理学，并有助于建立靶向治疗方法。然而，在断言遗传修饰剂是所有SCD表型的原因时需要谨慎，因为还有其他因素，如人群的遗传背景，环境成分，社会经济学和心理学，可以在临床异质性中发挥重要作用。
More than half a century after the discovery of the molecular basis of Sickle Cell Disease (SCD), the causes of the phenotypic heterogeneity of the disease remain unclear. This heterogeneity manifests with different clinical outcomes such as stroke, vaso-occlusive episodes, acute chest syndrome, avascular necrosis, leg ulcers, priapism and retinopathy. These outcomes cannot be explained by the single mutation in the beta-globin gene alone but may be attributed to genetic modifiers and environmental effects. Recent advances in the post human genome sequence era have opened the door for the identification of novel genetic modifiers in SCD. Studies are showing that phenotypes of SCD seem to be modulated by polymorphisms in genes that are involved in inflammation, cell–cell interaction and modulators of oxidant injury and nitric oxide biology. The discovery of genes implicated in different phenotypes will help understanding of the physiopathology of the disease and aid in establishing targeted cures. However, caution is needed in asserting that genetic modifiers are the cause of all SCD phenotypes, because there are other factors such as genetic background of the population, environmental components, socio-economics and psychology that can play significant roles in the clinical heterogeneity.