Journal Article

Predictive value of haptoglobin genotype as a risk of cerebral vasospasm after aneurysmal subarachnoid hemorrhage

El-Nabi, Sobhy Hassab, Fahmy, Nagia Aly, Geba, Khaled Mohammed, Khalaf, Magdy, Ibrahim, Mahmoud Haroon, Ateia, Ahmed Mohammed, Elbassiouny, Ahmed, El-Garawani, Islam

2020

Overview

•Cerebral vasospasm contributes to morbidity in subarachnoid hemorrhage.•Identifying genomics predicting risk of vasospasm offers novel therapeutic avenues.•Hp-2 allele was found to be an independent predictor of cerebral vasospasm. 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. 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. 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). 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.

• Publisher: Elsevier B.V,Elsevier Limited
• Subject: Age / Alleles / Aneurysm / Aneurysms / Cardiovascular disease / Cardiovascular diseases / Consciousness / Deoxyribonucleic acid / Diabetes / Diabetes mellitus / DNA / Genetic testing / Genotype & phenotype / Genotypes / Genotyping / Haptoglobin / Hemoglobin / Hyperlipidemia / Hypertension / Ischemia / Laboratories / Neurology / Neurosurgery / Patients / Population / Risk factors / Stroke / Subarachnoid hemorrhage / Ultrasound / Vascular diseases / Vasoconstriction / Vasospasm / Veins & arteries