The University of Southampton
University of Southampton Institutional Repository
Warning ePrints Soton is experiencing an issue with some file downloads not being available. We are working hard to fix this. Please bear with us.

Haptoglobin genotype and outcome after spontaneous intracerebral haemorrhage

Haptoglobin genotype and outcome after spontaneous intracerebral haemorrhage
Haptoglobin genotype and outcome after spontaneous intracerebral haemorrhage
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 and the single nucleotide polymorphism rs2000999 influences their levels; the HP1 allele is hypothesized to improve outcome after intracerebral haemorrhage (ICH). We investigated the associations of the HP CNV genotype and rs2000999 with haematoma volume, perihaematomal oedema (PHO) volume, and functional outcome as well as mortality after ICH.

Methods: We included patients with neuroimaging-proven intracerebral haemorrhage, available DNA, and six-month follow-up in an observational cohort study (CROMIS-2). We classified patients into three groups according to the HP CNV genotype: 1-1, 2-1 or 2-2 and also dichotomized 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 computed tomography; PHO was measured by oedema extension distance. Functional outcome was assessed by the modified Rankin score (mRS; 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 (n=608) mortality comparisons between HP groups, with HP2-2 as reference group, were as follows: OR HP1-1 0.73, 95% CI 0.34-1.56 (p-value=0.41) and OR HP2-1 0.5, 95% CI 0.28-0.89 (p-value=0.02) (overall p-value=0.06). We found no evidence of an 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.
MRI, cerebrovascular disease, congnition, stroke
0022-3050
298-304
Hostettler, Isabel C.
82239c37-f728-4295-bfe1-48b06a56fae3
Morton, Matthew J.
4a178059-af3c-4de6-9d69-4024ea6178dc
Ambler, Gareth
8025b7a7-77da-48db-8167-4349def61f7d
Kazmi, Nabila
ae4d2d4d-3133-4b29-aa08-ad526681ea9b
Gaunt, Tom R.
908f92b3-0c63-4f34-bee9-2351778a4e62
Wilson, Duncan
560ef552-7c8c-4437-9c76-e21a551520c5
Shakeshaft, Clare
00652f98-b63b-4918-bbc0-074ee903b580
Jäger, Hans R
4b30c0d1-db0d-4c8f-abef-924d9d843316
Cohen, Hannah
363cafe2-a74d-416e-8781-06a3ab130fda
Yousry, Tarek
6e37f93e-bee9-42bc-8be1-3d8b511051f9
Al-Shahi Salman, Rustam
4130f84c-5f4c-4c5e-9b0d-769c51f5cab3
Lip, Gregory Y.H.
0bd5d832-d4c4-42c5-8b6f-0289b3277fe5
Brown, Martin M.
10b1300d-23bc-48cc-8582-49d4b9454c94
Muir, Keith W.
c2a98f14-e4de-47e0-8ebd-c120ed08f7c5
Houlden, Henry
b4cd8392-164c-4d35-8933-690a804ebb18
Bulters, Diederik
f2080cef-122a-486d-925d-455316b8cd41
Galea, Ian
66209a2f-f7e6-4d63-afe4-e9299f156f0b
Werring, David J.
0caabc8a-8597-4f08-9189-e8a6e6a213a6
Hostettler, Isabel C.
82239c37-f728-4295-bfe1-48b06a56fae3
Morton, Matthew J.
4a178059-af3c-4de6-9d69-4024ea6178dc
Ambler, Gareth
8025b7a7-77da-48db-8167-4349def61f7d
Kazmi, Nabila
ae4d2d4d-3133-4b29-aa08-ad526681ea9b
Gaunt, Tom R.
908f92b3-0c63-4f34-bee9-2351778a4e62
Wilson, Duncan
560ef552-7c8c-4437-9c76-e21a551520c5
Shakeshaft, Clare
00652f98-b63b-4918-bbc0-074ee903b580
Jäger, Hans R
4b30c0d1-db0d-4c8f-abef-924d9d843316
Cohen, Hannah
363cafe2-a74d-416e-8781-06a3ab130fda
Yousry, Tarek
6e37f93e-bee9-42bc-8be1-3d8b511051f9
Al-Shahi Salman, Rustam
4130f84c-5f4c-4c5e-9b0d-769c51f5cab3
Lip, Gregory Y.H.
0bd5d832-d4c4-42c5-8b6f-0289b3277fe5
Brown, Martin M.
10b1300d-23bc-48cc-8582-49d4b9454c94
Muir, Keith W.
c2a98f14-e4de-47e0-8ebd-c120ed08f7c5
Houlden, Henry
b4cd8392-164c-4d35-8933-690a804ebb18
Bulters, Diederik
f2080cef-122a-486d-925d-455316b8cd41
Galea, Ian
66209a2f-f7e6-4d63-afe4-e9299f156f0b
Werring, David J.
0caabc8a-8597-4f08-9189-e8a6e6a213a6

Hostettler, Isabel C., Morton, Matthew J., Ambler, Gareth, Kazmi, Nabila, Gaunt, Tom R., Wilson, Duncan, Shakeshaft, Clare, Jäger, Hans R, Cohen, Hannah, Yousry, Tarek, Al-Shahi Salman, Rustam, Lip, Gregory Y.H., Brown, Martin M., Muir, Keith W., Houlden, Henry, Bulters, Diederik, Galea, Ian and Werring, David J. (2020) Haptoglobin genotype and outcome after spontaneous intracerebral haemorrhage. Journal of Neurology, Neurosurgery and Psychiatry, 91 (3), 298-304. (doi:10.1136/jnnp-2019-321774).

Record type: Article

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 and the single nucleotide polymorphism rs2000999 influences their levels; the HP1 allele is hypothesized to improve outcome after intracerebral haemorrhage (ICH). We investigated the associations of the HP CNV genotype and rs2000999 with haematoma volume, perihaematomal oedema (PHO) volume, and functional outcome as well as mortality after ICH.

Methods: We included patients with neuroimaging-proven intracerebral haemorrhage, available DNA, and six-month follow-up in an observational cohort study (CROMIS-2). We classified patients into three groups according to the HP CNV genotype: 1-1, 2-1 or 2-2 and also dichotomized 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 computed tomography; PHO was measured by oedema extension distance. Functional outcome was assessed by the modified Rankin score (mRS; 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 (n=608) mortality comparisons between HP groups, with HP2-2 as reference group, were as follows: OR HP1-1 0.73, 95% CI 0.34-1.56 (p-value=0.41) and OR HP2-1 0.5, 95% CI 0.28-0.89 (p-value=0.02) (overall p-value=0.06). We found no evidence of an 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.

Text
Hostettler et al postprint - Accepted Manuscript
Download (427kB)
Text
Hostettler et al 2019_postprint - Accepted Manuscript
Restricted to Repository staff only
Request a copy

More information

Accepted/In Press date: 28 October 2019
e-pub ahead of print date: 10 January 2020
Keywords: MRI, cerebrovascular disease, congnition, stroke

Identifiers

Local EPrints ID: 435362
URI: http://eprints.soton.ac.uk/id/eprint/435362
ISSN: 0022-3050
PURE UUID: 4cee81a6-4931-4036-b1c9-8bd801bbb379
ORCID for Matthew J. Morton: ORCID iD orcid.org/0000-0003-1986-0863
ORCID for Ian Galea: ORCID iD orcid.org/0000-0002-1268-5102

Catalogue record

Date deposited: 01 Nov 2019 17:30
Last modified: 26 Nov 2021 07:14

Export record

Altmetrics

Contributors

Author: Isabel C. Hostettler
Author: Matthew J. Morton ORCID iD
Author: Gareth Ambler
Author: Nabila Kazmi
Author: Tom R. Gaunt
Author: Duncan Wilson
Author: Clare Shakeshaft
Author: Hans R Jäger
Author: Hannah Cohen
Author: Tarek Yousry
Author: Rustam Al-Shahi Salman
Author: Gregory Y.H. Lip
Author: Martin M. Brown
Author: Keith W. Muir
Author: Henry Houlden
Author: Diederik Bulters
Author: Ian Galea ORCID iD
Author: David J. Werring

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×