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, 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.
MRI, cerebrovascular disease, congnition, stroke
298-304
Hostettler, Isabel C.
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Morton, Matthew J.
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Ambler, Gareth
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Kazmi, Nabila
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Gaunt, Tom R.
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Wilson, Duncan
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Shakeshaft, Clare
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Jäger, Hans R
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Cohen, Hannah
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Yousry, Tarek
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Al-Shahi Salman, Rustam
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Lip, Gregory Y.H.
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Brown, Martin M.
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Muir, Keith W.
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Houlden, Henry
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Bulters, Diederik
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Galea, Ian
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Werring, David J.
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1 March 2020
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
d6f9644a-a32f-45d8-b5ed-be54486ec21d
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), .
(doi:10.1136/jnnp-2019-321774).
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.
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Accepted/In Press date: 28 October 2019
e-pub ahead of print date: 10 January 2020
Published date: 1 March 2020
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© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.
Keywords:
MRI, cerebrovascular disease, congnition, stroke
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Local EPrints ID: 435362
URI: http://eprints.soton.ac.uk/id/eprint/435362
ISSN: 0022-3050
PURE UUID: 4cee81a6-4931-4036-b1c9-8bd801bbb379
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Date deposited: 01 Nov 2019 17:30
Last modified: 17 Mar 2024 03:51
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Contributors
Author:
Isabel C. Hostettler
Author:
Matthew J. Morton
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:
David J. Werring
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