Haptoglobin Genotype and Outcome after Subarachnoid Haemorrhage: New Insights from a Meta-Analysis

Abstract

Haptoglobin (Hp) is a plasma protein involved in clearing extracellular haemoglobin and regulating inflammation; it exists as two genetic variants (Hp1 and Hp2). In a meta-analysis of six published studies, we confirm that Hp genotype affects short-term outcome (cerebral vasospasm and/or delayed cerebral ischemia) after subarachnoid haemorrhage (SAH) but not long-term outcome (Glasgow Outcome Score and modified Rankin Scale between one and three months). A closer examination of the heterozygous group revealed that the short-term outcome of Hp2-1 individuals clustered with that of Hp1-1 and not Hp2-2, suggesting that the presence of one Hp1 allele was sufficient to confer protection. Since the presence of the Hp dimer is the only common feature between Hp1-1 and Hp2-1 individuals, the absence of this Hp moiety is most likely to underlie vasospasm in Hp2-2 individuals. These results have implications for prognosis after SAH and will inform further research into Hp-based mechanism of action and treatment.

Corrigendum to “Haptoglobin Genotype and Outcome after Subarachnoid Haemorrhage: New Insights from a Meta-Analysis”

“…This is achieved by stabilizing ferryl iron [16] and globin-based amino acid radicals [16, 17], sites within or close to the interface between Hp and Hb [18], preventing these reactive entities from participating in redox reactions. Second, Hp targets Hb for degradation, since Hb-Hp is recognized and cleared by CD163 [ 1 ]. Third, Hp induces an anti-inflammatory response (e.g., interleukin-10 secretion [19, 20]), which serves to balance Hb or heme-induced proinflammatory effects (e.g., tumour necrosis factor [21, 22] and interleukin-1 [23] secretion).…”

“…Haptoglobin (Hp) is an acute phase protein that binds to extracellular haemoglobin (Hb) with very high affinity. The resulting Hp-Hb complex is scavenged via CD163 expressed by cells of myeloid lineage [ 1 ]. There are two Hp alleles, Hp1 and Hp2.…”

“…In the article titled “Haptoglobin Genotype and Outcome after Subarachnoid Haemorrhage: New Insights from a Meta-Analysis” [ 1 ], there were errors that have been corrected in the revised version shown below.…”

Neuroprotective Role of the Nrf2 Pathway in Subarachnoid Haemorrhage and Its Therapeutic Potential

“…There are two different α alleles giving rise to three different phenotypes: α 1 α 1, α 1 α 2, and α 2 α 2 [108]. The Hp α 2 genotype has been shown to be associated with cerebral vasospasm [109–112], cerebral salt wasting [113], and poor outcome [113, 114]. In addition to the Hp-dependent pathway, there are other less efficient scavenging systems such as cubilin and megalin [115] and downstream haem clearance via the haemopexin-CD91 pathway [116].…”

Haptoglobin genotype and outcome after aneurysmal subarachnoid haemorrhage

“…Another unresolved question relates to the mechanism of action. HP alleles are associated with differential haptoglobin expression (HP1−1>HP2-1>HP2-210) as well as haemoglobin-haptoglobin complex scavenging rate by CD163 in vitro 1 11–13. It is not clear which of these two consequences of the HP CNV mediate its effect on aSAH outcome.…”