Skip to main content
SpringerLink
Log in

Haptoglobin Polymorphism and Association with Complications in Ghanaian Type 2 Diabetic Patients

  • Original Article
  • Published:
Indian Journal of Clinical Biochemistry Aims and scope Submit manuscript

Abstract

There is scanty information on the role of genetic factors, especially those relating to haptoglobin (Hp) phenotypes in the expression of complications among diabetes mellitus patients in Ghana. In this study, we investigated whether there is any association between Hp phenotypes and diabetic complications and to determine if association of the Hp phenotypes with diabetic complications in Ghanaian diabetics differ from those in Caucasians. A total of 398 participants were randomly recruited into the study. These comprised diabetic patients numbering 290 attending a diabetes Clinic in Ghana and 108 non-diabetic controls from the same community. Analyses of the results indicate that most of the diabetics with complications were of the Hp 2–2 (35%) and Hp 2–1 (23.9%) phenotypes. Fewer diabetics were found to be of the Hp 2–1 M phenotype. The controls were mostly of Hp 1–1 and Hp 2–1 M phenotypes. The odds ratio of having complications in a diabetic with an Hp 2–2 phenotype was 18.27 times greater than that for Hp 0–0. Hp 2–2 phenotype with its poor antioxidant activity may therefore be a useful predictor for the propensity of an individual to develop diabetes complications.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Haugen TH, Hanley JM, Health EC. Haptoglobin: a novel mode of biosynthesis of a liver secretory glucoprotein. J Biol Chem. 1981;256:1055–7.

    CAS  PubMed  Google Scholar 

  2. Bowman BH. Haptoglobin. In: Hepatic plasma proteins. San Diego, Academic Press; 1982. p. 159–67.

  3. Chiellini C, Bertacca A, Novelli SE, Gorgun CZ, Ciccarone A, Giordano A, Xu H, Soukas A, Costa M, Gandini D, Dimitri R, Bottone P, Cecchetti P, Pardini E, Perego L, Navalesi R, Folli F, Benzi L, Cinti S, Friedman JM, Hotamisligil GS, Maffei M. Obesity modulates the expression of haptoglobin in the white adipose tissue via TNF alpha. J Cell Physiol. 2002;190:251–8.

    Article  CAS  PubMed  Google Scholar 

  4. McGill JR, Yang F, Baldwin WD, Brune JL, Barnett DR, Bowman BH, Moore M. Localization of haptoglobin alpha and beta genes (HPA and HPB) to human chromosome 16q22 by insitu hybridization. Cytogenet Cell Genet. 1984;38:155–7.

    Article  CAS  PubMed  Google Scholar 

  5. Smithies O, Connell GE, Dixon GH. Inheritance of haptoglobin subtypes. Am J Hum Genet. 1962;14:14–21.

    CAS  PubMed  Google Scholar 

  6. Smithies O. Zone electrophoresis in starch gels: group variations in the serum proteins of normal human adults. Biochem J. 1955;61:629–41.

    CAS  PubMed  Google Scholar 

  7. Bensi G, Raugei G, Klefenz H, Cortese R. Structure and expression of human haptoglobin locus. EMBO J. 1985;4:119–26.

    CAS  PubMed  Google Scholar 

  8. Allison AC, Blumberg BS, Rees W. Haptoglobin types in British, Spanish Basque and Nigerian African Populations [letter]. Nature. 1958;181:824.

    Article  CAS  PubMed  Google Scholar 

  9. Harris H, Lawler SD, Smithies O. The occurrence of two unusual serum phenotypes in a single pedigree. Ann Hum Genet. 1960;24:63–9.

    Article  CAS  PubMed  Google Scholar 

  10. Koda Y, Soejima K, Yoshioka N, Kimura H. The haptoglobin-gene deletion responsible for anhaptoglobinemia. Am J Hum Genet. 1998;62:245–52.

    Article  CAS  PubMed  Google Scholar 

  11. Koda Y, Watanabe Y, Soejima K, Shimade E, Nishimura M, Morishita K, Moriya S, Mitsunaga S, Tadokoro K, Kimura H. Simple PCR detection of haptoglobin gene deletion in anhaptoglobinemic patients with antihaptogloibn antibody that causes anaphylactic transfusion reactions. Blood. 2000;95:1138–43.

    CAS  PubMed  Google Scholar 

  12. Teye K, Quaye IKE, Koda Y, Soejima M, Tsuneoka M, Pang H, Ekem I, Amoah AGB, Adjei A, Kimura H. A-61C and C-101G Hp gene promoter polymorphisms are respectively associated with ahaptoglobinaemia and hypohaptoglobinaemia in Ghana. Clin Genet. 2003;64:439–43.

    Article  CAS  PubMed  Google Scholar 

  13. Maeda N. DNA polymorphisms in the controlling region of human haptoglobin genes: a molecular explanation for the haptoglobin 2–1 modified phenotype. Am J Hum Genet. 1991;49:158–66.

    CAS  PubMed  Google Scholar 

  14. Chapelle JP, Albert A, Smeets JP, Heusghem C, Kulbertus HE. Effect of the haptoglobin phenotype on the size of a myocardial infarct. N Eng J Med. 1982;307:457–63.

    Article  CAS  Google Scholar 

  15. Langlois MR, Delangehe JR. Biological and clinical significance of haptoglobin polymorphism in humans. Clin Chem. 1996;42:1589–600.

    CAS  PubMed  Google Scholar 

  16. Bowman BH, Kurosky A. Haptoglobin: the evolutionary product of duplication, unequal crossing over, and point mutation. Adv Hum Genet. 1982;12:189–261.

    CAS  PubMed  Google Scholar 

  17. Melamed-Frank M, Lache O, Enav BI, Szafranek T, Levy NS, Ricklis RM, Levy AP. Structure-function analysis of the antioxidant properties of haptoglobin. Blood. 2001;98(13):3693–8.

    Article  CAS  PubMed  Google Scholar 

  18. Agil A, Fuller CJ, Jialal I. Susceptibility of plasma to ferrous iron/hydrogen peroxide-mediated oxidation: demonstration of a possible Fenton reaction. Clin Chem. 1995;41:220–5.

    CAS  PubMed  Google Scholar 

  19. Matsuoka H. Endothelial dysfunction associated with oxidative stress in human. Diabetes Res Clin Pract. 2001;54:65–72.

    Article  Google Scholar 

  20. Baynes JW. Role of oxidative stress in development of complications in diabetes. Diabetes. 1991;40:405–12.

    Article  CAS  PubMed  Google Scholar 

  21. Giugliano D, Eriello A, Paolosso G. Oxidative stress and diabetic vascular complications. Diabetes Care. 1996;19:257–67.

    Article  CAS  PubMed  Google Scholar 

  22. Halliwell B, Gutteridge JMC. Free radicals in biology and medicine. New York: Oxford University Press; 1989.

    Google Scholar 

  23. Asleh R, Marsh S, Shilkrut M, Binah O, Guetta J, Lejbkowicz F, Enav B, Shehadeh N, Kanter Y, Lache O, Cohen O, Levy N, Levy AP. Genetically determined heterogeneity in haemoglobin scavenging and susceptibility to diabetic cardiovascular disease. Circul Res. 2003;92:1193–200.

    Article  CAS  Google Scholar 

  24. Asleh R, Levy AP. In vivo and in vitro studies establishing haptoglobin as a major susceptibility gene for diabetic vascular disease. Vasc Health Risk Manag. 2005;1(1):19–28.

    Article  CAS  PubMed  Google Scholar 

  25. Adinortey MB, Gyan BA, Adjimani JP, Nyarko PE, Nyarko AK. Is there any relationship between haptoglobin phenotypes and retinopathy among Ghanaian diabetics? J Ghana Sci Ass. 2009;11(2):9–15.

    Google Scholar 

  26. Levy AP, Roguin A, Marsh S, Nakhoul FM, Herer P, Hochberg I, Skorecki K. Hp phenotypes and vascular complications in diabetes. N Engl J Med. 2003;343:969–75.

    Article  Google Scholar 

  27. Quaye IKE, Ababio G, Amoah AG. Haptoglobin 2–2 phenotype is a risk factor for Type-2-diabetes in Ghana. J Atheroscler Thromb. 2006;13(2):90–4.

    Article  PubMed  Google Scholar 

  28. WHO, Diabetes Mellitus. Technical Report Series. 1985; p. 727.

  29. Klein R, Klein BEK, Moss SE, DeMets DL. Proteinuria in diabetes. Arch Intern Med. 1988;148:181–6.

    Article  CAS  PubMed  Google Scholar 

  30. Nakhoul FM, Zoabi R, Kanter Y, Hochberg I, Leibu R, Miller B, Levy AP. Haptoglobin phenotype and diabetic nephropathy. Diabetologia. 2001;44:602–4.

    Article  CAS  PubMed  Google Scholar 

  31. Joint National Committee on prevention, detection, evaluation and treatment of high blood pressure. The sixth report of the joint national committee on prevention, detection, evaluation and treatment of high blood pressure (JNC VI). Arch Int Med 1997;157:2413–2446.

    Google Scholar 

  32. Robert N, Frank MD. Diabetic Retinopathy. N Engl J Med. 2004;350:48–58.

    Article  Google Scholar 

  33. Barham D, Trinder P. An improved colour reagent for the determination of blood glucose by oxidase system. Analyst. 1972;97:142–5.

    Article  CAS  PubMed  Google Scholar 

  34. Reitman S, Frankel SA. Colorimetric method for the determination of serum GOT and GPT. Am J Clin Pathol. 1957;28:57.

    Google Scholar 

  35. Giblet ER. Genetic markers in human blood. Oxford: Blackwell Scientific Publication; 1969.

    Google Scholar 

  36. Davis BJ. Disc electrophoresis II, method and application to human serum proteins. Ann NY Acad Sci. 1964;121:404–27.

    Article  CAS  PubMed  Google Scholar 

  37. Amoah AG, Owusu SK, Adjei S. Diabetes in Ghana: a community based prevalence study in Greater Accra. Diabetes Res Clin Pract. 2002;56(3):197–205.

    Article  PubMed  Google Scholar 

  38. Barroso I. Genetics of type 2 diabetes. Diabetic Med. 2005;22(5):517–35.

    Article  CAS  PubMed  Google Scholar 

  39. Knuiman MW, Welborn TA, McCann VJ, Stanton KG, Constable IJ. Prevalence of diabetic complications in relation to risk factors. Diabetes. 1986;35:1332–9.

    Article  CAS  PubMed  Google Scholar 

  40. Nyarko A, Adubofour K, Ofei F, Kpodonu J, Owusu S. Serum lipid and lipoprotein levels in Ghanaians with diabetes mellitus and hypertension. J Natl Med Assoc. 1997;89:191–6.

    CAS  PubMed  Google Scholar 

  41. Nyarko A, Asiedu-Larbi J, Ofosuhene M, Asare-Anane H, Addy ME. Serum lipids and antioxidants in Ghanaian diabetic, hypertensive and healthy subjects. Ghana Med J. 2003;37(2):72–82.

    Google Scholar 

  42. Stern MP, Ferrell RE, Rosenthal M, Haffner SM, Hazuda HP. Association between NIDDM, Rhesus blood group and haptoglobin phenotype. Results from the San Antonio Heart Study. Diabetes. 1986;35(4):387–91.

    Article  CAS  PubMed  Google Scholar 

  43. Awadallah S, Hamad M. The prevalence of type 2 diabetes mellitus is haptoglobin phenotype-independent. Cytobios. 2000;101(398):145–50.

    CAS  PubMed  Google Scholar 

  44. Nakhoul F, Marsh S, Hochberg I, Leibu R, Miller B, Levy AP. Haptoglobin phenotype and diabetic retinopathy. JAMA. 2000;284:1244–5.

    Article  CAS  PubMed  Google Scholar 

  45. Khan GA, Khan N, Ishaq M, Sastry EP, Rani TSH. Increased frequency of haptoglobin phenotype Hp 1–1 in diabetic patients with complications. Int J Diab Dev. 2002;22:101.

    Google Scholar 

  46. Bazzano LA, Serdula M, Liu S. Prevention of type 2 diabetes by diet and lifestyle modification. J Am College Nutr. 2005;24(5):310–9.

    Google Scholar 

  47. Okazaki T, Nagai T. Differences in haemoglobin binding ability of polymers among haptoglobin phenotypes. (Letter) Clin Chem 1997;43:2012–2013.

    Google Scholar 

  48. Brouwersa A, Langlois M, Delangheb J, Billieta J, De Buyzerec M, Vercaemsta R, Rietzschelc E, Bernarda D, Blatona V. Oxidized low-density lipoprotein, iron stores and haptoglobin polymorphism. Atherosclerosis. 2004;176:189–95.

    Article  Google Scholar 

  49. Balla G, Jacobs HS, Eaton JW, Belcher JD, Vercellotti GM. Hemin: a possible physiological mediator of low density lipoprotein oxidation and endothelia injury. Arterioscler Thromb. 1991;11:1700–11.

    Article  CAS  PubMed  Google Scholar 

  50. Bernard D, Christopher A, Delanghe J, Langlois M, De Buyzere M, Comhaire F. The effect of supplementation with an antioxidant preparation on LDL-oxidation is determined by haptoglobin polymorphism. Redox Rep. 2003;8:41–6.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We wish to thank Dr. I. K. Quaye of University of Ghana Medical School for assistance in the identification of Haptoglobin phenotypes and also constructive criticism during bench work. The authors wish to sincerely thank Mrs Comfort Opoku, Head of Laboratory, Mr Robert Wedzi, Mrs Gloria Adisusa, and Miss Patience Asumani for support during sample collection and Grace Ababio of University of Ghana Medical School for technical assistance. Appreciation also goes to Israel D. Agorsor of the Molecular Biology and Biotechnology department, university of Cape Coast for his constructive criticism after reading the manuscript.

Author information

Authors and Affiliations

  1. Department of Biochemistry, School of Biological Sciences, University of Cape Coast, Cape Coast, Ghana

    Michael B. Adinortey

  2. Immunology Department, Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Accra, Ghana

    Ben A. Gyan

  3. Department of Biochemistry, University of Ghana, Legon, Accra, Ghana

    Jonathan P. Adjimani

  4. Regional Institute for Population Studies, University of Ghana, Legon, Accra, Ghana

    Philomena E. Nyarko

  5. Tema General Hospital, Ghana Health Service, Tema, Ghana

    Charity Sarpong & Francis Y. Tsikata

  6. Clinical Pathology Department, Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Accra, Ghana

    Alexander K. Nyarko

Authors
  1. Michael B. Adinortey
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ben A. Gyan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jonathan P. Adjimani
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Philomena E. Nyarko
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Charity Sarpong
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Francis Y. Tsikata
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Alexander K. Nyarko
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael B. Adinortey.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Adinortey, M.B., Gyan, B.A., Adjimani, J.P. et al. Haptoglobin Polymorphism and Association with Complications in Ghanaian Type 2 Diabetic Patients. Ind J Clin Biochem 26, 366–372 (2011). https://doi.org/10.1007/s12291-011-0141-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12291-011-0141-3

Keywords

Search

Navigation