{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T10:50:39Z","timestamp":1761821439178,"version":"3.37.3"},"reference-count":40,"publisher":"BMJ","issue":"3","funder":[{"name":"Medical Research Council","award":["102215\/2\/13\/2"],"award-info":[{"award-number":["102215\/2\/13\/2"]}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C18281\/A19169"],"award-info":[{"award-number":["C18281\/A19169"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/L01453X\/1"],"award-info":[{"award-number":["MR\/L01453X\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Neurol Neurosurg Psychiatry"],"accepted":{"date-parts":[[2019,10,28]]},"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Haptoglobin is a haemoglobin-scavenging protein that binds and neutralises free haemoglobin and modulates inflammation and endothelial progenitor cell function. A<jats:italic>HP<\/jats:italic>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<jats:italic>HP<\/jats:italic>CNV genotype and rs2000999 with haematoma volume, perihaematomal oedema (PHO) volume, functional outcome and mortality after ICH.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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<jats:italic>HP<\/jats:italic>CNV: 1\u20131, 2\u20131 or 2\u20132 and also dichotomised<jats:italic>HP<\/jats:italic>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\u20136).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We included 731 patients (mean age 73.4, 43.5% female). Distribution of<jats:italic>HP<\/jats:italic>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%\u2009CI 0.34 to 1.56 (p value=0.41) and OR HP2-1 0.5, 95%\u2009CI 0.28 to 0.89 (p value=0.02) (overall p value=0.06). We found no evidence of association of<jats:italic>HP<\/jats:italic>CNV or rs200999 with functional outcome, ICH volume or PHO volume.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The HP2-1 genotype might be associated with lower 6-month mortality after ICH; this finding merits further study.<\/jats:p><\/jats:sec>","DOI":"10.1136\/jnnp-2019-321774","type":"journal-article","created":{"date-parts":[[2020,1,10]],"date-time":"2020-01-10T15:03:08Z","timestamp":1578668588000},"page":"298-304","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Haptoglobin genotype and outcome after spontaneous intracerebral haemorrhage"],"prefix":"10.1136","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9004-2540","authenticated-orcid":false,"given":"Isabel Charlotte","family":"Hostettler","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew 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