SICKLE-CELL-ANEMIA - BETA(S)-GENE CLUSTER HAPLOTYPES AS GENETIC-MARKERS FOR SEVERE DISEASE EXPRESSION
SICKLE-CELL-ANEMIA - BETA(S)-GENE CLUSTER HAPLOTYPES AS GENETIC-MARKERS FOR SEVERE DISEASE EXPRESSION
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DOI：
10.1001/archpedi.1993.02160350071011
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发表时间：
1993-11-01
影响因子：
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通讯作者：
HITI, A
中科院分区：
文献类型：
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作者：
POWARS, D;HITI, A
鉴定β (S)基因簇单倍型和α基因状态为镰状细胞性贫血高危患者的检测提供了有用的工具。长期临床病程与上述参数的关系分析显示，塞内加尔单倍型患者的严重程度较低，贝宁单倍型患者的严重程度中等，中非共和国（CAR）单倍型患者的临床表现最严重。α -地中海贫血-2的共遗传会进一步调节临床病程。在非洲和美国，CAR β (S)单倍型增加了早期发生并发症和死亡的风险（相对风险为2.25；95%置信区间为1.41至3.87）。CAR单倍型的检测可识别镰状细胞性贫血儿童，其镰状细胞性贫血有快速发展为镰状细胞性微血管病变的风险，最终在生命的前30年导致不可逆的器官损伤。对于CAR单倍型患者，在器官衰竭临床表现明显之前，应在儿童时期认真考虑潜在的治愈性治疗，如骨髓移植或基因插入。
Identification of the beta(S) gene cluster haplotype and alpha-gene status provides a useful tool for the detection of high-risk patients with sickle cell anemia. Analysis of the relationship of the long-term clinical course to the above parameters has revealed that those with the haplotype designated Senegal have decreased severity, those with the Benin haplotype have intermediate severity, and those with the Central African Republic (CAR) haplotype have the most severe clinical expression. Further modulation of the clinical course occurs with the coinheritance of alpha-thalassemia-2. In both Africa and the United States, the CAR beta(S) haplotype increased the risk (relative risk, 2.25; 95% confidence interval, 1.41 to 3.87) of developing a complication and death at an early age. Detection of the CAR haplotype identifies the child with sickle cell anemia at risk for a rapid rate of progression of sickle-induced microvasculopathy, ultimately leading to irreversible organ damage during the first three decades of life. In patients with the CAR haplotype, potential curative therapy, such as bone marrow transplantation or gene insertion, should be seriously considered during childhood, before organ failure is clinically evident.