Clinical Neurology and Neurosurgery 199 (2020) 106296
Available online 7 October 2020
0303-8467/© 2020 Elsevier B.V. All rights reserved.
Predictive value of haptoglobin genotype as a risk of cerebral vasospasm
after aneurysmal subarachnoid hemorrhage
Ahmed Mohammed Ateia
a,
*, Ahmed Elbassiouny
b
, Sobhy Hassab El-Nabi
c
, Nagia Aly Fahmy
d
,
Mahmoud Haroon Ibrahim
d
, Islam El-Garawani
c
, Khaled Mohammed Geba
c
, Magdy Khalaf
a
a
Department of Neurology, El Matareya Educational Hospital, Egypt
b
Department of Intervention Neurology, Faculty of Medicine, Ain Shams University, Egypt
c
Department of Zoology, Molecular Biology and Genetics Unit, Faculty of Science, Menoufa University, Egypt
d
Department of Neurology, Faculty of Medicine, Ain Shams University, Egypt
A R T I C L E INFO
Keywords:
Subarachnoid hemorrhage
Haptoglobin
Vasospasm
ABSTRACT
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 stratifcation 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) exami-
nation 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 signifcant 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 signifcant association for developing CV. Regarding
the poor Fisher scale and poor Hunt and Hess score both showed signifcant association with CV (P < 0.05).
Genotyping of Hp protein among our study cohort revealed that the relative distribution of the three haptoglobin
genotypes (Hp11, HP2-I & HP22) 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 radio-
graphic vasospasm detected by TCD among the studied patients (22 & 21 Vs 11: 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 devel-
opment of DCI; both variables failed to achieve a signifcant 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 stratifcation by allowing for the identifcation 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.
1. Introduction
In a systematic review of population-based studies, the incidence of
aneurysmal subarachnoid hemorrhage (aSAH) ranged from 2 to 16 per
100,000 population. Furthermore, the incidence rate of aSAH in low- to
middle-income countries was found to be nearly double that of high-
* Corresponding author at: Department of Neurology, Neuro-intervention Unit, Matareya Educational Hospital, Matareya, Cairo, 11719, Egypt.
E-mail addresses: a_ateia@hotmail.com (A.M. Ateia), ahmedelbassiony@gmail.com (A. Elbassiouny), sobhyhassab2001@yahoo.com (S.H. El-Nabi), dr.
nagiafahmy@med.asu.edu.eg (N.A. Fahmy), balkimy60@hotmail.com (M.H. Ibrahim), dr.garawani@yahoo.com (I. El-Garawani), khaledspain@yahoo.com
(K.M. Geba), magdymassoud@hotmail.com (M. Khalaf).
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Clinical Neurology and Neurosurgery
journal homepage: www.elsevier.com/locate/clineuro
https://doi.org/10.1016/j.clineuro.2020.106296
Received 28 December 2019; Received in revised form 4 October 2020; Accepted 6 October 2020