Haptoglobin genotype and functional outcome after aneurysmal subarachnoid hemorrhage

Clinical article

Ellen Kantor B.S.N.1, Hülya Bayır M.D.2, Dianxu Ren M.D., Ph.D.3, J. Javier Provencio M.D.4, Laura Watkins M.D.2, Elizabeth Crago R.N., Ph.D.1, Michael B. Horowitz M.D.5, Robert E. Ferrell Ph.D.6, Yvette P. Conley Ph.D.3,6, and Sheila A. Alexander Ph.D., R.N.1,2
View More View Less
  • 1 Department of Acute and Tertiary Care, School of Nursing;
  • | 2 Department of Critical Care Medicine;
  • | 3 Health and Community Systems, School of Nursing, University of Pittsburgh, Pennsylvania;
  • | 4 Neuroinflammation Research Center/Cerebrovascular Center, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio;
  • | 5 Neurological Surgery and Radiology, Center for Cranial Nerve Disorders, and Endovascular Therapy; and
  • | 6 Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania
Restricted access

Purchase Now

USD  $45.00

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $515.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $612.00
Print or Print + Online

Object

Haptoglobin allele heterogeneity has been implicated in differential reactive oxidant inhibition and inflammation. Haptoglobin α2-α2 has a lower affinity for binding hemoglobin, and when bound to hemoglobin, is cleared less easily by the body. The authors hypothesized that haptoglobin α2-α2 genotype should be less protective for downstream injury after aneurysmal subarachnoid hemorrhage (aSAH) and should portend a worse outcome.

Methods

Patients with Fisher Grade 2 or higher aSAH were enrolled in the study. Genotyping for haptoglobin genotype was performed from blood and/or CSF. Demographic information, medical condition variables, and hospital course were abstracted from the medical record upon enrollment into the study. Outcome data (modified Rankin Scale score, Glasgow Outcome Scale score, and mortality) were collected at 3 months posthemorrhage.

Results

The authors enrolled 193 patients who ranged in age from 18 to 75 years. Only Caucasians were used in this analysis to minimize bias from variable haptoglobin allele frequencies in populations of different ancestral backgrounds. The sample had more women than men (overall mean age 54.45 years). Haptoglobin α2 homozygotes were older than the other individuals in the study sample (57.27 vs 53.2 years, respectively; p = 0.02) and were more likely to have Fisher Grade 3 SAH (p = 0.02). Haptoglobin α2-α2 genotype, along with Fisher grade and Hunt and Hess grade, was associated with a worse 3-month outcome compared to those with the haptoglobin α1-α1 genotype according to modified Rankin Scale score after controlling for covariates (OR 4.138, p = 0.0463).

Conclusions

Patients with aSAH who carry the haptoglobin α2-α2 genotype had a worse outcome. Interestingly, the presence of a single α-2 allele was associated with worse outcome, suggesting that the haptoglobin α-2 protein may play a role in the pathology of brain injury following aSAH, although the mechanism for this finding requires further research. The haptoglobin genotype may provide additional information on individual risk of secondary injury and recovery to guide care focused on improving outcomes.

Abbreviations used in this paper:

aSAH = aneurysmal subarachnoid hemorrhage; GOS = Glasgow Outcome Scale; Hgb = hemoglobin; Hp = haptoglobin; mRS = modified Rankin Scale.

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $515.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $612.00
  • 1

    Alexander S, , Poloyac S, , Hoffman L, , Gallek M, , Ren Dianxu, & Balzer J, et al.: Endothelial nitric oxide synthase tagging single nucleotide polymorphisms and recovery from aneurysmal subarachnoid hemorrhage. Biol Res Nurs 11:4252, 2009

    • Search Google Scholar
    • Export Citation
  • 2

    Alvarez-Blasco F, , Martínez-García MA, , Luque-Ramírez M, , Parraza N, , San Millán JL, & Escobar-Morreale HF: Role of haptoglobin in polycystic ovary syndrome (PCOS), obesity and disorders of glucose tolerance in premenopausal women. PLoS ONE 4:e5606, 2009

    • Search Google Scholar
    • Export Citation
  • 3

    Borsody M, , Burke A, , Coplin W, , Miller-Lotan R, & Levy A: Haptoglobin and the development of cerebral artery vasospasm after subarachnoid hemorrhage. Neurology 66:634640, 2006

    • Search Google Scholar
    • Export Citation
  • 4

    Carter K, & Worwood M: Haptoglobin: a review of the major allele frequencies worldwide and their association with diseases. Int J Lab Hemtaol 29:92110, 2007

    • Search Google Scholar
    • Export Citation
  • 5

    Chaichana KL, , Levy AP, , Miller-Lotan R, , Shakur S, & Tamargo RJ: Haptoglobin 2-2 genotype determines chronic vasospasm after experimental subarachnoid hemorrhage. Stroke 38:32663271, 2007

    • Search Google Scholar
    • Export Citation
  • 6

    Delanghe J, , Allcock K, , Langlois M, , Claeys L, & De Buyzere M: Fast determination of haptoglobin phenotype and calculation of hemoglobin binding capacity using high pressure gel permeation chromatography. Clin Chim Acta 291:4351, 2000

    • Search Google Scholar
    • Export Citation
  • 7

    Delanghe JR, , Langlois MR, , De Buyzere ML, & Torck MA: Vitamin C deficiency and scurvy are not only a dietary problem but are codetermined by the haptoglobin polymorphism. Clin Chem 53:13971400, 2007

    • Search Google Scholar
    • Export Citation
  • 8

    Fisher CM, , Kistler JP, & Davis JM: Relation of cerebral vasospasm to subarachnoid hemorrhage visualized by computerized tomographic screening. Neurosurgery 6:19, 1980

    • Search Google Scholar
    • Export Citation
  • 9

    Froehler MT, , Kooshkabadi A, , Miller-Lotan R, , Blum S, , Sher S, & Levy A, et al.: Vasospasm after subarachnoid hemorrhage in haptoglobin 2-2 mice can be prevented with a glutathione peroxidase mimetic. J Clin Neurosci 17:11691172, 2010

    • Search Google Scholar
    • Export Citation
  • 10

    Hop JW, , Rinkel GJ, , Algra A, & van Gijn J: Case-fatality rates and functional outcome after subarachnoid hemorrhage: a systematic review. Stroke 28:660664, 1997

    • Search Google Scholar
    • Export Citation
  • 11

    Kistler JP, , Crowell RM, , Davis KR, , Heros R, , Ojemann RG, & Zervas T, et al.: The relation of cerebral vasospasm to the extent and location of subarachnoid blood visualized by CT scan: a prospective study. Neurology 33:424436, 1983

    • Search Google Scholar
    • Export Citation
  • 12

    Koch W, , Latz W, , Eichinger M, , Roguin A, , Levy AP, & Schömig A, et al.: Genotyping of the common haptoglobin Hp 1/2 polymorphism based on PCR. Clin Chem 48:13771382, 2002

    • Search Google Scholar
    • Export Citation
  • 13

    Langlois MR, & Delanghe JR: Biological and clinical significance of haptoglobin polymorphism in humans. Clin Chem 42:15891600, 1996

  • 14

    Levy AP, , Asleh R, , Blum S, , Levy NS, , Miller-Lotan R, & Kalet-Litman S, et al.: Haptoglobin: basic and clinical aspects. Antioxid Redox Signal 12:293304, 2010

    • Search Google Scholar
    • Export Citation
  • 15

    Lim SK, , Ferraro B, , Moore K, & Halliwell B: Role of haptoglobin in free hemoglobin metabolism. Redox Rep 6:219227, 2001

  • 16

    Miller SA, , Dykes DD, & Polesky HF: A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215, 1988

    • Search Google Scholar
    • Export Citation
  • 17

    Momin EN, , Schwab KE, , Chaichana KL, , Miller-Lotan R, , Levy AP, & Tamargo RJ: Controlled delivery of nitric oxide inhibits leukocyte migration and prevents vasospasm in haptoglobin 2-2 mice after subarachnoid hemorrhage. Neurosurgery 65:937945, 2009

    • Search Google Scholar
    • Export Citation
  • 18

    Qureshi AI, , Suri MF, , Yahia AM, , Suarez JI, , Guterman LR, & Hopkins LN, et al.: Risk factors for subarachnoid hemorrhage. Neurosurgery 49:607613, 2001

    • Search Google Scholar
    • Export Citation
  • 19

    Sadrzadeh SM, & Bozorgmehr J: Haptoglobin phenotypes in health and disorders. Am J Clin Pathol 121:Suppl S97S104, 2004

  • 20

    Smithies O, & Walker NF: Notation for serum-protein groups and the genes controlling their inheritance. Nature 178:694695, 1956

  • 21

    Teunissen LL, , Rinkel GJ, , Algra A, & van Gijn J: Risk factors for subarachnoid hemorrhage: a systematic review. Stroke 27:544549, 1996

  • 22

    Wassell J: Haptoglobin: function and polymorphism. Clin Lab 46:547552, 2000

Metrics

All Time Past Year Past 30 Days
Abstract Views 301 84 4
Full Text Views 299 12 0
PDF Downloads 216 5 0
EPUB Downloads 0 0 0