ElAlfy Mohsen Saleh, Ebeid Fatma Soliman Elsayed, Kamal Tarek Mostafa, Eissa Deena Samir, Ismail Eman Abdel Rahman, Mohamed Samar Hassan
Pediatrics Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Medical Genetics Pediatric Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
J Stroke Cerebrovasc Dis. 2019 Feb;28(2):441-449. doi: 10.1016/j.jstrokecerebrovasdis.2018.10.019. Epub 2018 Nov 5.
Cerebrovascular stroke is a common critical complication of sickle cell disease (SCD). Angiotensinogen (AGT) M235T gene polymorphism is associated with risk of ischemic stroke and cardiovascular disease.
We investigated the potential association between angiotensinogen M235T gene polymorphism and susceptibility to cerebrovascular and cardiopulmonary complications in adolescents with SCD.
Forty-six patients with SCD in steady state were studied stressing on history of stroke, hydroxyurea/chelation therapy, hematological profile, and echocardiographic findings. Polymerase chain reaction-based restriction fragment length polymorphism analysis was used to detect AGT M235T gene polymorphism. Fifty sex- and age-matched healthy controls were enrolled for assessment of M235T gene polymorphism pattern.
The distribution of AGT M235T gene polymorphism was similar between SCD patients and healthy controls. The frequency of T allele of AGT M235T gene polymorphism (TT and MT genotypes) was significantly higher among patients with history of manifest stroke (P < .001). Patients with TT and MT genotypes had higher incidence of cardiopulmonary complications (P = .041) as well as higher percentage of HbS (P < .001) and lower hemoglobin level (P = .008) compared with those with MM genotype. Serum ferritin, liver iron concentration, and cardiac T2* were not related to T alleles or genotypes. Logistic regression analysis revealed that M235T genotype was a significant independent factor related to the occurrence of stroke among patients with SCD (Odds Ratio 14.05, 95% confidence interval 3.82-28.91; P = .001).
AGT M235T gene polymorphism may represent a genetic modifier to vascular morbidities in Egyptian patients with SCD.
脑血管卒中是镰状细胞病（SCD）常见的严重并发症。血管紧张素原（AGT）M235T基因多态性与缺血性卒中和心血管疾病风险相关。
我们研究了血管紧张素原M235T基因多态性与SCD青少年脑血管和心肺并发症易感性之间的潜在关联。
对46例病情稳定的SCD患者进行研究，重点关注卒中病史、羟基脲/螯合疗法、血液学特征和超声心动图检查结果。采用基于聚合酶链反应的限制性片段长度多态性分析检测AGT M235T基因多态性。纳入50名年龄和性别匹配的健康对照，以评估M235T基因多态性模式。
SCD患者和健康对照之间AGT M235T基因多态性分布相似。有明显卒中病史的患者中，AGT M235T基因多态性的T等位基因（TT和MT基因型）频率显著更高（P <.001）。与MM基因型患者相比，TT和MT基因型患者的心肺并发症发生率更高（P = 0.041），HbS百分比更高（P <.001），血红蛋白水平更低（P = 0.008）。血清铁蛋白、肝脏铁浓度和心脏T2*与T等位基因或基因型无关。逻辑回归分析显示，M235T基因型是SCD患者卒中发生的显著独立相关因素（比值比14.05，95%置信区间3.82 - 28.91；P = 0.001）。
AGT M235T基因多态性可能是埃及SCD患者血管疾病的遗传修饰因子。
