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Observational Study
. 2020 Mar;91(3):298-304.
doi: 10.1136/jnnp-2019-321774. Epub 2020 Jan 10.

Haptoglobin genotype and outcome after spontaneous intracerebral haemorrhage

Isabel Charlotte Hostettler  1 , Matthew J Morton  2 , Gareth Ambler  3 , Nabila Kazmi  4 , Tom Gaunt  4 , Duncan Wilson  1 , Clare Shakeshaft  1 , H R Jäger  5 , Hannah Cohen  6 , Tarek A Yousry  5 , Rustam Al-Shahi Salman  7 , Gregory Lip  8 , Martin M Brown  1 , Keith Muir  9 , Henry Houlden  10 , Diederik O Bulters  11 , Ian Galea  12 , David J Werring  13 ; CROMIS-2 collaborators
Collaborators, Affiliations
Observational Study

Haptoglobin genotype and outcome after spontaneous intracerebral haemorrhage

Isabel Charlotte Hostettler et al. J Neurol Neurosurg Psychiatry. 2020 Mar.

Abstract

Objective: Haptoglobin 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.

Methods: We 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).

Results: We 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.

Conclusion: The HP2-1 genotype might be associated with lower 6-month mortality after ICH; this finding merits further study.

Keywords: MRI; cerebrovascular disease; congnition; stroke.

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Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1. Patient selection flow diagram
Figure 2
Figure 2
A) Differences in OED in Haptoglobin genotype and SNP, B) Differences in ICH volume in Haptoglobin genotype and SNP
See this image and copyright information in PMC

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