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Haptoglobin Polymorphisms Are Associated with Crohn’s Disease, Disease Behavior, and Extraintestinal Manifestations in Hungarian Patients

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Abstract

Functional differences and association with inflammatory disorders were found relating to three major haptoglobin (Hp) phenotypes. Our aim was to investigate Hp polymorphisms in Hungarian patients with Crohn’s disease (CD). Four hundred sixty-eight CD patients and 384 healthy controls were examined. Hp phenotypes were determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting of the sera. The frequency of the Hp1 allele was significantly higher in CD (0.395; OR, 1.24; 95% CI, 1.02–1.52; P=0.03) compared to controls (0.345). In CD, Hp phenotype was associated with disease behavior (OR [Hp2‐1 vs other], 2.06; 95% CI, 1.29–3.28 for inflammatory behavior). Furthermore, an increased frequency of primary sclerosing cholangitis was observed in the Hp 2-2 compared to the Hp 1-1 phenotype (6.5% vs. 0.0%; P=0.039). We conclude that the Hp polymorphism is associated with CD, inflammatory disease behavior, and primary sclerosing cholangitis in Hungarian patients. Further studies are required to evaluate the significance of Hp polymorphisms in other populations from geographically diverse regions.

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References

  1. Podolsky DK (2002) Inflammatory bowel disease. N Engl J Med 347:417–429

    Article  PubMed  CAS  Google Scholar 

  2. Ahmad T, Tamboli CP, Jewell D, Colombel JF (2004) Clinical relevance of advances in genetics and pharmacogenetics of IBD. Gastroenterology 126:1533–1549

    Article  PubMed  CAS  Google Scholar 

  3. Sadrzadeh SM, Bozorgmehr J (2004) Haptoglobin phenotypes in health and disorders. Am J Clin Pathol 121 (Suppl):S97–S104

    PubMed  Google Scholar 

  4. Langlois MR, Delanghe JR (1996) Biological and clinical significance of haptoglobin polymorphism in humans. Clin Chem 42:1589–1600

    PubMed  CAS  Google Scholar 

  5. Wassell J (2000) Haptoglobin: function and polymorphism. Clin Lab 46:547–552

    PubMed  CAS  Google Scholar 

  6. Arredouani M, Matthijs P, Van Hoeyveld E, Kasran A, Baumann H, Ceuppens JL, Stevens E (2003) Haptoglobin directly affects T cells and suppresses T helper cell type 2 cytokine release. Immunology 108:144–151

    Article  PubMed  CAS  Google Scholar 

  7. Xie Y, Li Y, Zhang Q, Stiller MJ, Wang CL, Streilein JW (2000) Haptoglobin is a natural regulator of Langerhans cell function in the skin. J Dermatol Sci 24:25–37

    Article  PubMed  CAS  Google Scholar 

  8. El-Ghmati SM, Arredouani M, Van Hoeyveld EM, Ceuppens JL, Stevens EA (2002) Haptoglobin interacts with the human mast cell line HMC-1 and inhibits its spontaneous proliferation. Scand J Immunol 55:352–358

    Article  PubMed  CAS  Google Scholar 

  9. Levy AP (2003) Genetics of diabetic cardiovascular disease: identification of a major susceptibility gene. Acta Diabetol Suppl 2:S330–S333

    Article  Google Scholar 

  10. Kristiansen M, Graversen JH, Jacobsen C, Sonne O, Hoffman HJ, Law SK, Moestrup SK (2001) Identification of the haemoglobin scavenger receptor. Nature 409:198–201

    Article  PubMed  CAS  Google Scholar 

  11. Langlois M, Delanghe J, Philippe J, Ouyang J, Bernard D, De Buyzere M, Van Nooten G, Leroux-Roels G (1997) Distribution of lymphocyte subsets in bone marrow and peripheral blood is associated with haptoglobin type. Binding of haptoglobin to the B-cell lectin CD22. Eur J Clin Chem Clin Biochem 35:199–205

    PubMed  CAS  Google Scholar 

  12. Lakatos L, Mester G, Erdelyi Z, Balogh M, Szipocs I, Kamaras G, Lakatos PL (2004) Striking elevation in the incidence and prevalence of inflammatory bowel disease in a province of Western Hungary between 1977-2001. World J Gastroenterol 10:404–409

    PubMed  Google Scholar 

  13. Lakatos PL, Lakatos L, Szalay F, Willheim-Polli C, Osterreicher C, Tulassay Z, Molnar T, Reinisch W, Papp J, Mozsik G, Ferenci P, Hungarian IBD Study Group (2005) Toll-like receptor 4 and NOD2/CARD15 mutations in Hungarian patients with Crohn’s disease: phenotype-genotype correlations. World J Gastroenterol 11:1489–1495

    PubMed  CAS  Google Scholar 

  14. Lennard-Jones JE (1989) Classification of inflammatory bowel disease. Scand J Gastroenterol Suppl 170:2–6, discussion 16–19

    PubMed  CAS  Google Scholar 

  15. Munkholm P, Langholz E, Davidsen M, Binder V (1994) Frequency of glucocorticoid resistance and dependency in Crohn’s disease. Gut 35:360–362

    PubMed  CAS  Google Scholar 

  16. Gasche C, Scholmerich J, Brynskov J, D’Haens G, Hanauer SB, Irvine EJ, Jewell DP, Rachmilewitz D, Sachar DB, Sandborn WJ, Sutherland LR (2000) A simple classification of Crohn’s disease: report of the Working Party for the World Congresses of Gastroenterology, Vienna 1998. Inflamm Bowel Dis 6:8–15

    Article  PubMed  CAS  Google Scholar 

  17. Yang SE, Min WK, Park H, Chun S, Nah J, Kim JQ (2000) Distribution of haptoglobin phenotypes in a Korean population, using the semi-automated PhastSystem. Ann Clin Biochem 37:205–209

    Article  PubMed  Google Scholar 

  18. Tauszik T, Szabo L (1992) Haptoglobin polymorphism in Hungary. Gene Geogr 6:153–157

    PubMed  CAS  Google Scholar 

  19. Shanahan F (2002) Crohn’s disease. Lancet 359:62–69

    Article  PubMed  CAS  Google Scholar 

  20. Bottini N, Gloria-Bottini F, Amante A, Saccucci P, Bottini E (2005) Genetic polymorphism and TH1/TH2 orientation. Int Arch Allergy Immunol 138:328–333

    Article  PubMed  CAS  Google Scholar 

  21. Talwalkar JA, Lindor KD (2005) Primary sclerosing cholangitis. Inflamm Bowel Dis 11:62–72

    Article  PubMed  Google Scholar 

  22. Aoki CA, Bowlus CL, Gershwin ME (2005) The immunobiology of primary sclerosing cholangitis. Autoimmun Rev 4:137–143

    Article  PubMed  CAS  Google Scholar 

  23. Cameron RG, Blendis LM, Neuman MG (2001) Accumulation of macrophages in primary sclerosing cholangitis. Clin Biochem 34:195–201

    Article  PubMed  CAS  Google Scholar 

  24. Wiencke K, Spurkland A, Schrumpf E, Boberg KM (2001) Primary sclerosing cholangitis is associated to an extended B8-DR3 haplotype including particular MICA and MICB alleles. Hepatology 34:625–630

    PubMed  CAS  Google Scholar 

  25. Orchard T (2003) Extraintestinal complications of inflammatory bowel disease. Curr Gastroenterol Rep 5:512–517

    PubMed  Google Scholar 

  26. Lakatos L, Pandur T, David G, Balogh Z, Kuronya P, Tollas A, Lakatos PL (2003) Association of extraintestinal manifestations of inflammatory bowel disease (IBD) in a province of Western Hungary with disease phenotype: results of a 25-year follow-up study. World J Gastroenterol 9:2300–2307

    PubMed  Google Scholar 

  27. Kasvosve I, Gomo ZA, Mvundura E, Moyo VM, Saungweme T, Khumalo H, Gordeuk VR, Boelaert JR, Delanghe JR, De Bacquer D, Gangaidzo IT (2000) Haptoglobin polymorphism and mortality in patients with tuberculosis. Int J Tuberc Lung Dis 4:771–775

    PubMed  CAS  Google Scholar 

  28. Ubaidullaev AM, Kazakov KS, Khakimov MA (2002) Genetic variants of haptoglobin in patients with nephrotuberculosis. Probl Tuberk 7:42–43

    PubMed  Google Scholar 

  29. Eisaev BA (1995) Results of the treatment of patients with recurrence of pulmonary tuberculosis with different types of haptoglobin. Probl Tuberk 6:20–22

    PubMed  Google Scholar 

Download references

Acknowledgments

This research was supported by a Mecenatura (11/2005) grant. We would like to express our most sincere gratitude to Andrea Bezi and Maria Fabian for their assistance with the laboratory work.

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Authors and Affiliations

  1. Department of Gastroenterology, University of Debrecen, Nagyerdei krt. 98, H-4012, Debrecen, Hungary

    Maria Papp, Karoly Palatka, Ildiko Foldi, Istvan Tornai, Zsuzsanna Vitalis & Istvan Altorjay

  2. First Department of Medicine, Semmelweis University, Budapest, Hungary

    Peter Laszlo Lakatos & Janos Papp

  3. Department of Hematology, University of Debrecen, Debrecen, Hungary

    Miklos Udvardy

  4. Clinical Research Center, University of Debrecen, Debrecen, Hungary

    Jolan Harsfalvi

  5. First Department of Surgery, University of Debrecen, Debrecen, Hungary

    Tamas Dinya

  6. First Department of Medicine, Erzsebet Hospital, Budapest, Hungary

    Agota Kovacs

  7. First Department of Medicine, University of Szeged, Szeged, Hungary

    Tamas Molnar

  8. Department of Gastroenterology, St. Margit Hospital, Budapest, Hungary

    Pal Demeter

  9. First Department of Medicine, Csolnoky F. County Hospital, Veszprem, Hungary

    Laszlo Lakatos

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  1. Maria Papp
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  13. Janos Papp
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Hungarian IBD Study Group

Corresponding author

Correspondence to Maria Papp.

Additional information

Maria Papp and Peter Laszlo Lakatos contributed equally to this work and both should be considered first authors.

Further Hungarian IBD Study Group members are Peter Fuszek, Henrik Csaba Horvath, Peter Vargha, Simon Fischer, and Janos Osztovits, First Department of Medicine, Semmelweis University, Budapest; Laszlo Bene, First Department of Medicine, Erzsebet Hospital, Budapest; Ferenc Nagy and Janos Lonovics, First Department of Medicine, University of Szeged, Szeged; Levente Balint, Ferenc Huoranszky, and Istvan Dobo, Department of Gastroenterology and Surgery, St. Margit Hospital, Budapest; Zsolt Tulassay, Laszlo Herszenyi, Pal Miheller, and Annamaria Nemeth, Second Department of Medicine, Semmelweis University, Budapest; Gyorgy Szekely, First Department of Medicine, Szent Janos Hospital, Budapest; and Zsuzsanna Erdelyi, Gabor Mester, Csaba Molnar, and Tunde Pandur, First Department of Medicine, Csolnoky F. County Hospital, Veszprem.

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Papp, M., Lakatos, P.L., Hungarian IBD Study Group. et al. Haptoglobin Polymorphisms Are Associated with Crohn’s Disease, Disease Behavior, and Extraintestinal Manifestations in Hungarian Patients. Dig Dis Sci 52, 1279–1284 (2007). https://doi.org/10.1007/s10620-006-9615-1

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  • DOI: https://doi.org/10.1007/s10620-006-9615-1

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