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An Analysis of Haptoglobin Genotypes and Recovery from Aneurysmal Subarachnoid Hemorrhage

Kantor, Ellen (2010) An Analysis of Haptoglobin Genotypes and Recovery from Aneurysmal Subarachnoid Hemorrhage. Undergraduate Thesis, University of Pittsburgh. (Unpublished)

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Background: Haptoglobin (Hp) binds hemoglobin (Hgb), thereby inhibiting free radical production. It is presumed that Hp 2-2 genotype is associated with worse functional outcome after aneurysmal subarachnoid hemorrhage (aSAH) related to the weaker affinity for Hgb binding, decreased clearance of hemoglobin from the site of hemorrhage, and an associated increase in secondary injury with the alpha-2 allele.Objective: The objective is to describe the relationship between Hp genotype and mortality and gross functional outcome after aSAH.Methods: A total sample of 268 subjects was narrowed down to a sample of 193 Caucasian subjects (due to differences in allele frequency distribution among races), age 18-75 with a diagnosis of aSAH, Fisher Grade greater than or equal to 2, DNA and outcome data available and without pre-existing chronic neurologic disease/deficit were enrolled into an ongoing study (NR004339). Demographic and medical condition variables were extracted from medical records. Modified Rankin Score (MRS) and Glasgow Outcome Score (GOS) were assessed at 3, 6, 12, and 24 months after aSAH. Data analysis included univariate analysis as well as multivariate logistic regression analysis, controlling for covariates including age, sex, and severity of hemorrhage (Fisher grade).Results: The sample was primarily female (n=138; 71.5%) and Caucasian (n=237; 88.4%) with a mean age of 54.45 years. This sample was further narrowed down to include only subjects of Caucasian race due to differences in allele frequency distribution among other races previously published in literature. Haptoglobin 2-2 genotype was significantly correlated with MRS at 3 months post aSAH during univariate analysis (p=.04) and at 3 months after controlling for covariates in the multivariate logistic regression analysis (p=.05). Univariate analysis produced a significant (p=.02) relationship between subjects whose genotypes yielded at least one alpha-2 allele and development of cerebral vasospasm (CV). Subjects whose genotypes had only one alpha-2 allele were significantly (p=.01) associated with Fisher grade. Fisher grade and Hunt and Hess score were both significantly associated with poor outcomes on MRS at all four time periods. Age was significantly (p=.01) correlated with Hp 1-1 and Hp 1-2 genotypes; specifically, these patients were younger than those with Hp 2-2 genotype. After controlling for covariates, Fisher grade was the only covariate that maintained significance in predicting outcomes after aSAH at all four time periods.Conclusions: Subjects whose genotypes contain at least one alpha-2 allele more often had poor outcomes on MRS at 3 months post aSAH and were more likely to develop CV. Additionally, haptoglobin genotype can be used as predictor of gross functional outcome when measured using MRS at 3 months after aSAH. The Fisher grading scale and Hunt and Hess scoring system are both significantly useful for predicting outcomes (GOS, MRS, mortality) at all four time periods after aSAH.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee MemberRen, Dianxudir8@pitt.eduDIR8
Committee MemberBayir, Hülyabayihx@upmc.eduHUB22
Committee MemberProvencio, J.
Committee MemberAlexander, Sheila Asalexand@pitt.eduSALEXAND
Committee MemberConley, Yvette Pyconley@pitt.eduYCONLEY
Date: 23 August 2010
Date Type: Completion
Defense Date: 21 July 2010
Approval Date: 23 August 2010
Submission Date: 4 August 2010
Access Restriction: 5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
Institution: University of Pittsburgh
Schools and Programs: School of Nursing > Nursing
David C. Frederick Honors College
Degree: BSN - Bachelor of Science in Nursing
Thesis Type: Undergraduate Thesis
Refereed: Yes
Uncontrolled Keywords: cerebral vasospasm; Fisher grade; Glasgow outcome score; Hunt and Hess score; Modified Rankin Scale
Other ID:, etd-08042010-175546
Date Deposited: 10 Nov 2011 19:57
Last Modified: 19 Dec 2016 14:37


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