Tang D C, Prauner R, Liu W, Kim K H, Hirsch R P, Driscoll M C, Rodgers G P
Molecular and Clinical Hematology Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA.
Am J Hematol. 2001 Nov;68(3):164-9. doi: 10.1002/ajh.1173.
Stroke is one of the most devastating complications of patients with sickle cell disease (SCD). Currently, there are no known molecular or genetic markers that can be used to assess the risk of stroke in this population. We have previously shown that relative hypertension may be one risk factor for stroke in SCD. In a case-control study, we investigated the association between GT-repeat polymorphism within the angiotensinogen (AGT) gene and the risk of stroke in pediatric patients with SCD. After informed consent was obtained, 63 patients (21 stroke subjects and 42 nonstroke control subjects matched according to age and sex) with SCD followed at local pediatric hematology clinics were genotyped to test the association of specific GT-repeat alleles of the AGT gene and occurrence of stroke. There were statistical differences in the distribution of the genotypes among stroke and nonstroke SCD patients (chi(2) = 10.82, df = 11, P < 0.05). We also found GT-repeat alleles A3 and/or A4 of the AGT gene conferred a four-fold increase in the risk of stroke (odds ratio [OR] = 4, P < 0.05). The attributable odds ratio for allele A3 and A4 is 2.24 and 4.33, respectively (P < 0.005). Our results suggest that GT-repeat within the AGT gene may be associated with risk of stroke in pediatric SCD. The relative risk of stroke in the presence of alleles A3 and/or A4 is fourfold greater than in the absence of these alleles. If these data are substantiated in a larger cohort of patients, our results indicate that the determination of GT-repeat of AGT gene may be a useful genetic marker to assess the risk for stroke of patients with SCD. Am. J. Hematol. 68:164-169, 2001. Published 2001 Wiley-Liss, Inc.
中风是镰状细胞病（SCD）患者最具破坏性的并发症之一。目前，尚无已知的分子或遗传标记可用于评估该人群的中风风险。我们之前已经表明，相对性高血压可能是SCD患者中风的一个风险因素。在一项病例对照研究中，我们调查了血管紧张素原（AGT）基因内GT重复多态性与小儿SCD患者中风风险之间的关联。在获得知情同意后，对当地儿科血液学诊所随访的63例SCD患者（21例中风患者和42例按年龄和性别匹配的非中风对照患者）进行基因分型，以检测AGT基因特定GT重复等位基因与中风发生之间的关联。中风和非中风SCD患者的基因型分布存在统计学差异（卡方=10.82，自由度=11，P<0.05）。我们还发现，AGT基因的GT重复等位基因A3和/或A4使中风风险增加了四倍（优势比[OR]=4，P<0.05）。等位基因A3和A4的归因优势比分别为2.24和4.33（P<0.005）。我们的结果表明，AGT基因内的GT重复可能与小儿SCD患者的中风风险相关。存在等位基因A3和/或A4时中风的相对风险比不存在这些等位基因时大四倍。如果这些数据在更大的患者队列中得到证实，我们的结果表明，测定AGT基因的GT重复可能是评估SCD患者中风风险的一个有用的遗传标记。《美国血液学杂志》68:164 - 169，2001年。2001年由威利 - 利斯公司出版。
