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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter / Tate, Jillian R.

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IMPACT FACTOR 2016: 3.432

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1437-4331
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Volume 51, Issue 8 (Aug 2013)

Issues

An enzyme linked immunosorbent assay (ELISA) for the determination of the human haptoglobin phenotype

Nina S. Levy
  • Technion-Institute of Technology, The Ruth and Bruce Rappaport Faculty of Medicine, Haifa, Israel
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Moshe Vardi
  • Technion-Institute of Technology, The Ruth and Bruce Rappaport Faculty of Medicine, Haifa, Israel
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Shany Blum
  • Technion-Institute of Technology, The Ruth and Bruce Rappaport Faculty of Medicine, Haifa, Israel
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Rachel Miller-Lotan
  • Technion-Institute of Technology, The Ruth and Bruce Rappaport Faculty of Medicine, Haifa, Israel
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Yefim Afinbinder
  • Technion-Institute of Technology, The Ruth and Bruce Rappaport Faculty of Medicine, Haifa, Israel
  • Yefim Afinbinder is deceased.
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Patricia A. Cleary / Andrew D. Paterson
  • Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto Ontario, Canada
  • Dalla Lana School of Public Health, University of Toronto, Ontario, Canada
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Bhupinder Bharaj
  • Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto Ontario, Canada
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/ Janet K. Snell-Bergeon / Marian J. Rewers / Orit Lache
  • Technion-Institute of Technology, The Ruth and Bruce Rappaport Faculty of Medicine, Haifa, Israel
  • Other articles by this author:
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/ Andrew P. Levy
  • Corresponding author
  • Technion-Israel Institute of Technology, 1 Efron Street, Bat Galim, POB 9649, Haifa 31096 Israel
  • Email
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Published Online: 2013-03-13 | DOI: https://doi.org/10.1515/cclm-2013-0018

Abstract

Background: Haptoglobin (Hp) is an abundant serum protein which binds extracorpuscular hemoglobin (Hb). Two alleles exist in humans for the Hp gene, denoted 1 and 2. Diabetic individuals with the Hp 2-2 genotype are at increased risk of developing vascular complications including heart attack, stroke, and kidney disease. Recent evidence shows that treatment with vitamin E can reduce the risk of diabetic vascular complications by as much as 50% in Hp 2-2 individuals. We sought to develop a rapid and accurate test for Hp phenotype (which is 100% concordant with the three major Hp genotypes) to facilitate widespread diagnostic testing as well as prospective clinical trials.

Methods: A monoclonal antibody raised against human Hp was shown to distinguish between the three Hp phenotypes in an enzyme linked immunosorbent assay (ELISA). Hp phenotypes obtained in over 8000 patient samples using this ELISA method were compared with those obtained by polyacrylamide gel electrophoresis or the TaqMan PCR method.

Results: Our analysis showed that the sensitivity and specificity of the ELISA test for Hp 2-2 phenotype is 99.0% and 98.1%, respectively. The positive predictive value and the negative predictive value for Hp 2-2 phenotype is 97.5% and 99.3%, respectively. Similar results were obtained for Hp 2-1 and Hp 1-1 phenotypes. In addition, the ELISA was determined to be more sensitive and specific than the TaqMan method.

Conclusions: The Hp ELISA represents a user-friendly, rapid and highly accurate diagnostic tool for determining Hp phenotypes. This test will greatly facilitate the typing of thousands of samples in ongoing clinical studies.

This article offers supplementary material which is provided at the end of the article.

Keywords: diabetes; ELISA; haptoglobin phenotype; pharmacogenomics; vitamin E

References

  • 1.

    Levy AP, Asleh R, Blum S, Levy NS, Miller-Lotan R, Kalet-Litman S, etal. Haptoglobin: basic and clinical aspects. Antioxid Redox Signal 2010;12:293–304.Web of SciencePubMedGoogle Scholar

  • 2.

    Vardi M, Blum S, Levy AP. Haptoglobin genotype and cardiovascular outcomes in diabetes mellitus – natural history of the disease and the effect of vitamin E treatment. Meta-analysis of the medical literature. Eur J Int Med 2012;23:628–32.Google Scholar

  • 3.

    Levy NS, Levy AP. ELISA for determination of the haptoglobin phenotype. Clin Chem 2004;50:2148–50.PubMedGoogle Scholar

  • 4.

    Wejman JC, Hovsepian D, Wall JS, Hainfeld JF, Greer J. Structure and assembly of haptoglobin polymers by electron microscopy. J Mol Biol 1984;174:343–68.Google Scholar

  • 5.

    Lee IM, Cook NR, Gaziano JM, Gordon D, Ridker PM, Manson JE, etal. Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women’s Health Study: a randomized controlled trial. J Am Med Assoc 2005;294:56–65.Google Scholar

  • 6.

    Dabelea D, Kinney G, Snell-Bergeon JK, Hokanson JE, Eckel RH, Ehrlich J, etal. Effect of type I diabetes on the gender difference in coronary artery calcification: a role for insulin resistance? The Coronary Artery Calcification in Type I Diabetes (CACTI) Study. Diabetes 2003;52:2833–9.PubMedGoogle Scholar

  • 7.

    Mauer M, Zinman B, Gardiner R, Suissa S, Sinaiko A, Strand T, etal. Renal and retinal effects of enalapril and losartan in type 1 diabetes. N Engl J Med 2009;361:40–51.Google Scholar

  • 8.

    Milman U, Blum S, Shapira C, Aronson D, Miller-Lotan R, Anbinder Y, etal. Vitamin E supplementation reduces cardiovascular events in a subgroup of middle-aged individuals with both type 2 diabetes mellitus and the haptoglobin 2-2 genotype: a prospective double-blinded clinical trial. Arterioscler Thromb Vasc Biol 2008;28:341–7.Web of ScienceGoogle Scholar

  • 9.

    Hatoum IJ, Hu FB, Nelson JJ, Rimm EB. Lipoprotein-associated phospholipase A2 activity and incident coronary heart disease among men and women with type 2 diabetes. Diabetes 2010;5:1239–43.PubMedGoogle Scholar

  • 10.

    Schnaider Beeri M, Goldbourt U, Silverman JM, Noy S, Schmeidler J, Ravona-Springer R, etal. Diabetes mellitus in midlife and the risk of dementia three decades later. Neurology 2004;63:1902–7.PubMedGoogle Scholar

  • 11.

    Diabetes Control and Complications Trial Research Group. The effect of intensive diabetes treatment on the development and progression of long-term complications in insulin-dependent diabetes mellitus: the Diabetes Control and Complications Trial. N Engl J Med 1993;329:978–86.Google Scholar

  • 12.

    Hochberg I, Roguin A, Nikolsky E, Chanderashekhar PV, Cohen S, Levy AP. Haptoglobin phenotype and coronary artery collaterals in diabetic patients. Atherosclerosis 2002;161:441–6.Google Scholar

  • 13.

    Soejima M, Koda Y. TaqMan-based real-time PCR for genotyping common polymorphisms of haptoglobin (HP1 and HP2). Clin Chem 2008;54:1908–13.Web of ScienceGoogle Scholar

  • 14.

    Blum S, Vardi M, Brown JB, Russell A, Milman U, Shapira C, etal. Vitamin E reduces cardiovascular disease in individuals with diabetes mellitus and the haptoglobin 2-2 genotype. Pharmacogenomics 2010;11:675–84.Web of SciencePubMedGoogle Scholar

  • 15.

    Melamed-Frank M, Lache O, Enav BI, Szafranek T, Levy NS, Ricklis RM, etal. Structure-function analysis of the antioxidant properties of haptoglobin. Blood 2001;98:3693–8.Google Scholar

  • 16.

    Asleh R, Marsh S, Shilkrut M, Binah O, Guetta J, Lejbkowicz F, etal. Genetically determined heterogeneity in hemoglobin scavenging and susceptibility to diabetic cardiovascular disease. Circ Res 2003;92:1193–200.PubMedGoogle Scholar

  • 17.

    Asleh R, Blum S, Kalet-Litman S, Alsheik J, Miller-Lotan R, Asaf R, etal. Correction of HDL dysfunction in individuals with diabetes and the haptoglobin 2-2 genotype. Diabetes 2008;57:2794–800.Web of SciencePubMedGoogle Scholar

  • 18.

    Miller ER 3rd, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 2005;142:37–46.Google Scholar

About the article

Corresponding author: Andrew P. Levy, Technion-Israel Institute of Technology, 1 Efron Street, Bat Galim, POB 9649, Haifa 31096, Israel, Phone: +972-4-8295202, Fax: +972-4-8514103


Received: 2013-01-06

Accepted: 2013-02-18

Published Online: 2013-03-13

Published in Print: 2013-08-01


Citation Information: Clinical Chemistry and Laboratory Medicine, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2013-0018.

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