Presence of Haptoglobin-2 Allele Is Associated with Worse Functional Outcomes After Spontaneous Intracerebral Hemorrhage

Murthy, Santosh B.; Levy, Andrew P.; Duckworth, Joshua K.; Schneider, Eric B.; Shalom, Hadar; Hanley, Daniel F.; Tamargo, Rafael J.; Nyquist, Paul

doi:10.1016/j.wneu.2014.12.013

Cited by 21 publications

(23 citation statements)

References 19 publications

(14 reference statements)

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“…We confirmed previous results showing evidence towards increased mortality with HP2-2 18 , but did not observe a unidirectional dose response of HP alleles in a direction of increasing or decreasing mortality across HP genotypes (mortality: HP1-1 18.2%; HP2-1 12.6%; HP2-2…”

Section: Discussionsupporting

confidence: 91%

“…In this large prospective, multicentre cohort study, HP was not associated with functional outcome as assessed by the mRS. The HP CNV distribution was comparable to that reported in a previous study, apart from a slightly higher proportion of HP1-1 patients and lower proportion of HP2-2 18 . Despite the larger sample size, we could not replicate this previous study's finding of an association of the HP2 allele with functional outcome 18 .…”

Section: Discussionsupporting

confidence: 86%

“…ICH and PHO volume have been demonstrated to influence functional outcome 18 19 . A previous study reported worse functional outcome for patients with HP2 allele (HP2-1 or 2-2) compared to HP1-1 patients as well as some evidence for increased mortality for each HP2 allele 18 . The HP CNV might be associated with functional outcome after ICH through differences in haemoglobin clearance and protection from the cytotoxic and inflammatory effects of haemoglobin breakdown products.…”

Section: Introductionmentioning

confidence: 91%

“…Three different HP CNV genotypes exist: HP1-1, HP2-1 and HP2-2, and their respective protein products differ in molecular size and haemoglobin-binding capacity [15][16][17] . A previous study demonstrated some evidence that patients with the HP2 allele have a larger haematoma volume, though the underlying mechanisms remain unknown 18 . An increase in haematoma volume may be accompanied by more perihaematomal oedema (PHO) 18 19 .…”

Section: Introductionmentioning

confidence: 99%

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Haptoglobin genotype and outcome after spontaneous intracerebral haemorrhage

Hostettler

Morton

Ambler

et al. 2020

J Neurol Neurosurg Psychiatry

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ObjectiveHaptoglobin 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.MethodsWe 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).ResultsWe 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.ConclusionThe HP2-1 genotype might be associated with lower 6-month mortality after ICH; this finding merits further study.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Haptoglobin genotype and outcome after spontaneous intracerebral haemorrhage

Hostettler

Morton

Ambler

et al. 2020

J Neurol Neurosurg Psychiatry

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“…58 In addition to candidate gene studies, a genome-wide complex trait analysis using data from GWA analyses calculated that apart from 59 A recent study found an association between a haptoglobin allele variant and lower odds of favorable modified Rankin Scale (described as modified Rankin Scale score 0-2) outcome. 60 Also genetic factors influencing intermediate ICH risk factors may influence outcome because a report showed that a genetic risk score based on 42 single nucleotide polymorphisms related to blood pressure was related to poor clinical outcome at 90 days specifically for individuals with deep ICH.…”

Section: Ich and Recoverymentioning

confidence: 99%

Stroke Recovery Genetics

Lindgren

Maguire

2016

Stroke

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Influences of genetic variants on stroke recovery: a meta-analysis of the 31,895 cases

et al. 2019

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Background The influences of genetic variants on functional clinical outcomes following stroke are unclear. In order to reliably quantify these influences, we undertook a comprehensive meta-analysis of outcomes after acute intracerebral haemorrhage (ICH) or ischaemic stroke (AIS) in relation to different genetic variants. Methods PubMed, PsycInfo, Embase and Medline electronic databases were searched up to January 2019. Outcomes, defined as favourable or poor, were assessed by validated scales (Barthel index, modified Rankin scale, Glasgow outcome scale and National Institutes of Health stroke scale). Results Ninety-two publications comprising 31,895 cases met our inclusion criteria. Poor outcome was observed in patients with ICH who possessed the APOE4 allele: OR =2.60 (95% CI = 1.25-5.41, p = 0.01) and in AIS patients with the GA or AA variant at the BDNF-196 locus: OR = 2.60 (95% CI = 1.25-5.41, p = 0.01) or a loss of function allele of CYP2C19: OR = 2.36 (95% CI = 1.56-3.55, p < 0.0001). Poor outcome was not associated with APOE4: OR = 1.02 (95% CI = 0.81-1.27, p = 0.90) or IL6-174 G/C: OR = 2.21 (95% CI = 0.55-8.86, p = 0.26) in patients with AIS. Conclusions We demonstrate that recovery of AIS was unfavourably associated with variants of BDNF and CYP2C19 genes whilst recovery of ICH was unfavourably associated with APOE4 gene.

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Presence of Haptoglobin-2 Allele Is Associated with Worse Functional Outcomes After Spontaneous Intracerebral Hemorrhage

Cited by 21 publications

References 19 publications

Haptoglobin genotype and outcome after spontaneous intracerebral haemorrhage

Haptoglobin genotype and outcome after spontaneous intracerebral haemorrhage

Stroke Recovery Genetics

Influences of genetic variants on stroke recovery: a meta-analysis of the 31,895 cases

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