Haptoglobin genotype and outcome after spontaneous intracerebral haemorrhage. Issue 3 (10th January 2020)

• Record Type: Journal Article
• Authors: Hostettler, Isabel Charlotte; Morton, Matthew J; Ambler, Gareth; Kazmi, Nabila; Gaunt, Tom; Wilson, Duncan; Shakeshaft, Clare; Jäger, H R; Cohen, Hannah; Yousry, Tarek A; Al-Shahi Salman, Rustam; Lip, Gregory; Brown, Martin M; Muir, Keith; Houlden, Henry; Bulters, Diederik O; Galea, Ian; Werring, David J
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Walstow Deborah author non-byline.; Watchurst Caroline author non-byline.; Watson Fran author non-byline.; Waugh Dean author non-byline.; Wilkinson Peter author non-byline.; Wilson David author non-byline.; Wilson-Owen Sarah author non-byline.; Wroath Belinda author non-byline.; Wynter Inez author non-byline.; Young Emma author non-byline.;
• Is Part Of: Journal of neurology, neurosurgery and psychiatry. Volume 91:Issue 3(2020)
• Page Start: 298
• Page End: 304
• Publication Date: 2020-01-10
• Subjects: stroke -- MRI -- congnition -- cerebrovascular disease; Neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; Psychiatry -- Periodicals; 616.8
• DOI: 10.1136/jnnp-2019-321774
• Languages: English
• ISSNs: 0022-3050

Abstract

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.