Biomaterial Database

Haptoglobin genotype and outcome after aneurysmal subarachnoid haemorrhage. 2020

Matthew J Morton, and Isabel C Hostettler, and Nabila Kazmi, and Varinder S Alg, and Stephen Bonner, and Martin M Brown, and Andrew Durnford, and Benjamin Gaastra, and Patrick Garland, and Joan Grieve, and Neil Kitchen, and Daniel Walsh, and Ardalan Zolnourian, and Henry Houlden, and Tom R Gaunt, and Diederik O Bulters, and David J Werring, and Ian Galea, and

Clinical Neurosciences, Clinical & Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, Hampshire, UK.

After aneurysmal subarachnoid haemorrhage (aSAH), extracellular haemoglobin (Hb) in the subarachnoid space is bound by haptoglobin, neutralising Hb toxicity and helping its clearance. Two exons in the HP gene (encoding haptoglobin) exhibit copy number variation (CNV), giving rise to HP1 and HP2 alleles, which influence haptoglobin expression level and possibly haptoglobin function. We hypothesised that the HP CNV associates with long-term outcome beyond the first year after aSAH. The HP CNV was typed using quantitative PCR in 1299 aSAH survivors in the Genetics and Observational Subarachnoid Haemorrhage (GOSH) Study, a retrospective multicentre cohort study with a median follow-up of 18 months. To investigate mediation of the HP CNV effect by haptoglobin expression level, as opposed to functional differences, we used rs2000999, a single nucleotide polymorphism associated with haptoglobin expression independent of the HP CNV. Outcome was assessed using modified Rankin and Glasgow Outcome Scores. SAH volume was dichotomised on the Fisher grade. Haemoglobin-haptoglobin complexes were measured in cerebrospinal fluid (CSF) of 44 patients with aSAH and related to the HP CNV. The HP2 allele associated with a favourable long-term outcome after high-volume but not low-volume aSAH (multivariable logistic regression). However rs2000999 did not predict outcome. The HP2 allele associated with lower CSF haemoglobin-haptoglobin complex levels. The CSF Hb concentration after high-volume and low-volume aSAH was, respectively, higher and lower than the Hb-binding capacity of CSF haptoglobin. The HP2 allele carries a favourable long-term prognosis after high-volume aSAH. Haptoglobin and the Hb clearance pathway are therapeutic targets after aSAH.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D002532	Intracranial Aneurysm	Abnormal outpouching in the wall of intracranial blood vessels. Most common are the saccular (berry) aneurysms located at branch points in CIRCLE OF WILLIS at the base of the brain. Vessel rupture results in SUBARACHNOID HEMORRHAGE or INTRACRANIAL HEMORRHAGES. Giant aneurysms (>2.5 cm in diameter) may compress adjacent structures, including the OCULOMOTOR NERVE. (From Adams et al., Principles of Neurology, 6th ed, p841)	Aneurysm, Cerebral,Aneurysm, Intracranial,Basilar Artery Aneurysm,Berry Aneurysm,Brain Aneurysm,Cerebral Aneurysm,Giant Intracranial Aneurysm,Mycotic Aneurysm, Intracranial,Aneurysm, Anterior Cerebral Artery,Aneurysm, Anterior Communicating Artery,Aneurysm, Basilar Artery,Aneurysm, Middle Cerebral Artery,Aneurysm, Posterior Cerebral Artery,Aneurysm, Posterior Communicating Artery,Anterior Cerebral Artery Aneurysm,Anterior Communicating Artery Aneurysm,Middle Cerebral Artery Aneurysm,Posterior Cerebral Artery Aneurysm,Posterior Communicating Artery Aneurysm,Aneurysm, Berry,Aneurysm, Brain,Aneurysm, Giant Intracranial,Aneurysm, Intracranial Mycotic,Aneurysms, Basilar Artery,Aneurysms, Berry,Aneurysms, Brain,Aneurysms, Cerebral,Aneurysms, Giant Intracranial,Aneurysms, Intracranial,Aneurysms, Intracranial Mycotic,Artery Aneurysm, Basilar,Artery Aneurysms, Basilar,Basilar Artery Aneurysms,Berry Aneurysms,Brain Aneurysms,Cerebral Aneurysms,Giant Intracranial Aneurysms,Intracranial Aneurysm, Giant,Intracranial Aneurysms,Intracranial Aneurysms, Giant,Intracranial Mycotic Aneurysm,Intracranial Mycotic Aneurysms,Mycotic Aneurysms, Intracranial
D002648	Child	A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL.	Children
D005260	Female		Females
D005838	Genotype	The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.	Genogroup,Genogroups,Genotypes
D006242	Haptoglobins	Plasma glycoproteins that form a stable complex with hemoglobin to aid the recycling of heme iron. They are encoded in man by a gene on the short arm of chromosome 16.	Haptoglobin
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000293	Adolescent	A person 13 to 18 years of age.	Adolescence,Youth,Adolescents,Adolescents, Female,Adolescents, Male,Teenagers,Teens,Adolescent, Female,Adolescent, Male,Female Adolescent,Female Adolescents,Male Adolescent,Male Adolescents,Teen,Teenager,Youths
D000328	Adult	A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available.	Adults