Driscoll M Catherine, Hurlet Anne, Styles Lori, McKie Virgil, Files Beatrice, Olivieri Nancy, Pegelow Charles, Berman Brian, Drachtman Richard, Patel Kantilal, Brambilla Donald
Department of Pediatrics, The George Washington University School of Medicine, Washington, DC, USA.
Blood. 2003 Mar 15;101(6):2401-4. doi: 10.1182/blood.V101.6.2401.
Cerebrovascular disease is a common cause of morbidity in sickle cell anemia (HbSS): approximately 10% of patients have a clinical stroke before 20 years of age, and another 22% have silent infarction on magnetic resonance imaging. The phenotypic variation among patients with HbSS suggests a role for modifier genes and/or environmental influences. To assess the familial component of clinical stroke in HbSS, we estimated the prevalence of clinical stroke among all patients and among HbSS sibling pairs at 9 pediatric centers. The sample included 3425 patients with sickle cell disease who were younger than 21 years, including 2353 patients with HbSS. The stroke prevalence was 4.9% for all genotypes; 7.1% for patients with HbSS; 1.1% for patients with HbSbeta(o) thalassemia; 0.6% for patients with Sbeta(+) thalassemia; and 0% for patients with HbSC. In 207 sibships, more than 1 child had HbSS. There were 42 sibships in which at least 1 sibling had a stroke, and in 10 of the 42, 2 siblings had a stroke. A permutation test indicated that the number of families in which 2 children had strokes was larger than the number expected if strokes were randomly distributed among children in sibships (P =.0012). There was no difference in stroke prevalence based on sex, nor was the mean age at stroke presentation significantly different between singletons and sibships with stroke. We conclude that there is a familial predisposition to stroke in HbSS. Attempts to identify genetic modifiers should be initiated with family-based studies.
脑血管疾病是镰状细胞贫血（HbSS）发病的常见原因：约10%的患者在20岁前发生临床中风，另有22%在磁共振成像上有无症状性梗死。HbSS患者之间的表型差异提示修饰基因和/或环境影响起了作用。为评估HbSS临床中风的家族因素，我们在9个儿科中心估计了所有患者以及HbSS同胞对中临床中风的患病率。样本包括3425名21岁以下的镰状细胞病患者，其中2353名是HbSS患者。所有基因型的中风患病率为4.9%；HbSS患者为7.1%；HbSβ（o）地中海贫血患者为1.1%；Sβ（+）地中海贫血患者为0.6%；HbSC患者为0%。在207个同胞关系中，不止1个孩子患有HbSS。有42个同胞关系中至少有1个兄弟姐妹发生了中风，在这42个中的10个中，2个兄弟姐妹都发生了中风。一项置换检验表明，2个孩子都发生中风的家庭数量多于中风在同胞关系中的孩子中随机分布时预期的数量（P = 0.0012）。基于性别，中风患病率没有差异，中风发病时的平均年龄在发生中风的单胎和同胞之间也没有显著差异。我们得出结论，HbSS存在中风的家族易感性。应从基于家庭的研究开始尝试识别基因修饰因子。
