• Isabel Charlotte Hostettler, Matthew J Morton, Gareth Ambler, Nabila Kazmi, Tom Gaunt, Duncan Wilson, Clare Shakeshaft, H R Jäger, Hannah Cohen, Tarek A Yousry, Rustam Al-Shahi Salman, Gregory Lip, Martin M Brown, Keith Muir, Henry Houlden, Diederik O Bulters, Ian Galea, David J Werring, and CROMIS-2 collaborators.
• Stroke Research Centre, University College London, Queen Square Institute of Neurology, London, UK.
• J. Neurol. Neurosurg. Psychiatr. 2020 Mar 1; 91 (3): 298-304.

ObjectiveHaptoglobin is a haemoglobin-scavenging protein that binds and neutralises free haemoglobin and modulates inflammation and endothelial progenitor cell function. A HP gene copy number variation (CNV) generates HP1 and HP2 alleles, while the single-nucleotide polymorphism rs2000999 influences their levels. The HP1 allele is hypothesised to improve outcome after spontaneous (non-traumatic) intracerebral haemorrhage (ICH). We investigated the associations of the HP CNV genotype and rs2000999 with haematoma volume, perihaematomal oedema (PHO) volume, functional outcome and mortality after ICH.MethodsWe included patients with neuroimaging-proven ICH, available DNA and 6-month follow-up in an observational cohort study (CROMIS-2). We classified patients into three groups according to the HP CNV: 1-1, 2-1 or 2-2 and also dichotomised HP into HP1-containing genotypes (HP1-1 and HP2-1) and HP2-2 to evaluate the HP1 allele. We measured ICH and PHO volume on CT; PHO was measured by oedema extension distance. Functional outcome was assessed by modified Rankin score (unfavourable outcome defined as mRS 3-6).ResultsWe included 731 patients (mean age 73.4, 43.5% female). Distribution of HP CNV genotype was: HP1-1 n=132 (18.1%); HP2-1 n=342 (46.8%); and HP2-2 n=257 (35.2%). In the multivariable model mortality comparisons between HP groups, HP2-2 as reference, were as follows: OR HP1-1 0.73, 95% CI 0.34 to 1.56 (p value=0.41) and OR HP2-1 0.5, 95% CI 0.28 to 0.89 (p value=0.02) (overall p value=0.06). We found no evidence of association of HP CNV or rs200999 with functional outcome, ICH volume or PHO volume.ConclusionThe HP2-1 genotype might be associated with lower 6-month mortality after ICH; this finding merits further study.© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

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