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

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.