Powars D R, Chan L, Schroeder W A
Department of Pediatrics, University of California School of Medicine, Los Angeles.
Am J Pediatr Hematol Oncol. 1990 Fall;12(3):367-74. doi: 10.1097/00043426-199023000-00022.
Restriction endonuclease analysis was used to detect alpha-gene deletions and to determine the haplotypes in the DNA of the beta S-gene-cluster [Benin, Central African Republic (CAR), and Senegal] in 221 patients with sickle cell anemia (SS). The clinical expression of SS was modified by the beta S-gene-cluster polymorphisms and the alpha-gene status (alpha-thalassemia-2). The overall risk of soft tissue organ failure caused by the obliterative sickle vasculopathy (including stroke, renal failure, chronic lung disease with cor pulmonale, leg ulcers, and young adult death) was increased threefold in those with a CAR haplotype and was decreased in those with a Senegalese chromosome (p = 0.003). In the presence of a Senegalese haplotype, the patient's health is better, and with the CAR haplotype it is always worse. With the Benin, it is intermediate. Acute recurrent clinical events including hospitalized sickle cell crisis, bone infarction, and infection are decreased in frequency in those with a Senegalese haplotype. The risk of most acute events including acute chest syndrome is equivalent in those with Benin or CAR haplotypes. In the United States, alpha-thalassemia-2 is co-inherited randomly among the beta S-gene-cluster haplotypes. Acute events occurring during childhood are minimally effected by this co-inheritance. The risk of soft tissue organ failure is decreased. After the age of 20 years, painful episodes of the lumbar dorsal area are increased in patients who had alpha-thalassemia-2 in association with degenerative bone disease.(ABSTRACT TRUNCATED AT 250 WORDS)
采用限制性内切酶分析检测221例镰状细胞贫血（SS）患者βS基因簇[贝宁、中非共和国（CAR）和塞内加尔]DNA中的α基因缺失并确定单倍型。SS的临床表型因βS基因簇多态性和α基因状态（α地中海贫血-2）而改变。具有CAR单倍型的患者发生闭塞性镰状血管病变导致软组织器官衰竭（包括中风、肾衰竭、慢性肺病伴肺心病、腿部溃疡和青年死亡）的总体风险增加了两倍，而具有塞内加尔染色体的患者风险降低（p=0.003）。存在塞内加尔单倍型时，患者健康状况较好；存在CAR单倍型时，健康状况总是较差。具有贝宁单倍型时，健康状况处于中间水平。具有塞内加尔单倍型的患者，包括住院镰状细胞危象、骨梗死和感染在内的急性复发性临床事件的发生频率降低。具有贝宁或CAR单倍型的患者发生包括急性胸综合征在内的大多数急性事件的风险相当。在美国，α地中海贫血-2在βS基因簇单倍型中随机共遗传。儿童期发生的急性事件受这种共遗传的影响最小。软组织器官衰竭的风险降低。20岁以后，合并退行性骨病的α地中海贫血-2患者腰背部疼痛发作增加。（摘要截短于250字）
