OBJECTIVE This study aims to investigate the genetic predisposition of haptoglobin (Hp) genotype as a predictor for cerebral vasospasm (CV) after acute subarachnoid hemorrhage (aSAH) in the Egyptian population. This permits CV risk factors stratification of patients with aSAH. Hence, it will guide the treatment plan and intensive monitoring for those patients. PATIENTS AND METHODS The study was carried out at El Matareya Teaching Hospital, Cairo, Egypt. We studied 50 patients with aSAH who were prospectively recruited and followed up by transcranial Doppler (TCD) examination for 14 days following aneurysmal rupture to early detect hemodynamic changes associated with CV and also the occurrence of delayed cerebral ischemia (DCI) as a secondary outcome. In this study, we attempted to analyze Hp genotyping as a potential predictor of CV and DCI during the acute phase of aneurysmal SAH. RESULTS As a part of result analyses, among studied patients, 34 patients (68 %) developed CV and 19 patients (38 %) developed DCI. Only history of hypertension [RR = 1.6 (OR = 4)], diabetes mellitus [RR = 1.5 (OR = 3.4)] and smoking [RR = 1.5 (OR = 3.6)] had a significant independent relationship (P < 0.05) with short term risk to develop CV following aSAH. While, Age, sex, hyperlipidemia, cardiovascular disease and peripheral vascular disease, intracranial aneurysm site and size did not achieve significant association for developing CV. Regarding the poor Fisher scale and poor Hunt and Hess score both showed significant association with CV (P < 0.05). Genotyping of Hp protein among our study cohort revealed that the relative distribution of the three haptoglobin genotypes (Hp1-1, HP2-I & HP2-2) among Egyptian patients of aSAH was 14 %, 40 % and 46 %, respectively; (gene proportion being 0.34 for Hp1 and 0.66 for Hp2). Furthermore; Hp 2 allele was associated with radiographic vasospasm detected by TCD among the studied patients (2-2 & 2-1 Vs 1-1: RR = 5.4, OR = 19.8, P < 0.001). In the regression model; Hp genotype expressing Hp-2 allele is predictive for higher risk of development of CV after aSAH. Moreover, searching for the relationship between CV & Hp genotype and the risk for development of DCI; both variables failed to achieve a significant relationship for DCI (P > 0.05). CONCLUSION The Hp genotype may determine the susceptibility to cerebral vasospasm after acute aSAH. This has the potential for use in risk stratification by allowing for the identification of those patients requiring intensive monitoring due to their inherent genetic risk for developing CV allowing for the promising selective application of aggressive treatments to those patients.

中文翻译：

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触珠蛋白基因型对动脉瘤性蛛网膜下腔出血后脑血管痉挛风险的预测价值

目的 本研究旨在调查触珠蛋白 (Hp) 基因型作为埃及人群急性蛛网膜下腔出血 (aSAH) 后脑血管痉挛 (CV) 预测因子的遗传易感性。这允许对 aSAH 患者进行心血管危险因素分层。因此，它将指导这些患者的治疗计划和强化监测。患者和方法 该研究在埃及开罗的 El Matareya 教学医院进行。我们研究了 50 名 aSAH 患者，这些患者被前瞻性招募并在动脉瘤破裂后进行 14 天的经颅多普勒 (TCD) 检查，以及早发现与 CV 相关的血流动力学变化以及延迟脑缺血 (DCI) 的发生作为次要结果。在这项研究中，我们试图分析 Hp 基因分型作为动脉瘤性 SAH 急性期 CV 和 DCI 的潜在预测因子。结果 作为结果分析的一部分，在研究的患者中，34 名患者 (68%) 发生了 CV，19 名患者 (38%) 发生了 DCI。只有高血压病史 [RR = 1.6 (OR = 4)]、糖尿病 [RR = 1.5 (OR = 3.4)] 和吸烟 [RR = 1.5 (OR = 3.6)] 与aSAH 后发生 CV 的短期风险。而年龄、性别、高脂血症、心血管疾病和外周血管疾病、颅内动脉瘤部位和大小与发生 CV 没有显着关联。关于较差的 Fisher 量表和较差的 Hunt 和 Hess 评分均与 CV 显着相关（P < 0.05）。我们研究队列中 Hp 蛋白的基因分型显示，埃及 aSAH 患者中三种触珠蛋白基因型（Hp1-1、HP2-I 和 HP2-2）的相对分布分别为 14%、40% 和 46%；（Hp1 的基因比例为 0.34，Hp2 的基因比例为 0.66）。此外; Hp 2 等位基因与 TCD 在研究患者中检测到的放射影像血管痉挛相关（2-2 和 2-1 Vs 1-1：RR = 5.4，OR = 19.8，P < 0.001）。在回归模型中；表达 Hp-2 等位基因的 Hp 基因型可预测 aSAH 后发生 CV 的更高风险。此外，寻找CV和Hp基因型与DCI发展风险之间的关系；两个变量都未能实现 DCI 的显着关系（P > 0.05）。结论 Hp基因型可能决定急性aSAH后脑血管痉挛的易感性。