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Clinical Chemistry 54: 697-704, 2008. First published February 7, 2008; 10.1373/clinchem.2007.098780
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(Clinical Chemistry. 2008;54:697-704.)
© 2008 American Association for Clinical Chemistry, Inc.

Molecular Diagnostics and Genetics

Haptoglobin Polymorphism: A Novel Genetic Risk Factor for Celiac Disease Development and Its Clinical Manifestations

Maria Papp1,a,1, Ildiko Foldi1,1, Eva Nemes2, Miklos Udvardy1, Jolan Harsfalvi3, Istvan Altorjay1, Istvan Mate1, Tamas Dinya4, Csaba Varvolgyi5, Zsolt Barta6, Gabor Veres7, Peter Laszlo Lakatos8, Judit Tumpek9, Laszlo Toth10, Erzsebet Szathmari11, Aniko Kapitany9, Agnes Gyetvai9 and Ilma R. Korponay-Szabo2,12

1 Second Department of Medicine, University of Debrecen, Debrecen, Hungary; 2 Department of Pediatrics, University of Debrecen, Debrecen, Hungary; 3 Clinical Research Center, University of Debrecen, Debrecen, Hungary; 4 First Department of Surgery, University of Debrecen, Debrecen, Hungary; 5 First Department of Medicine, University of Debrecen, Debrecen, Hungary; 6 Third Department of Medicine, University of Debrecen, Debrecen, Hungary; 7 First Department of Pediatrics, Semmelweis University, Budapest, Hungary; 8 First Department of Medicine, Semmelweis University, Budapest, Hungary; 9 Laboratory of Clinical Immunology, University of Debrecen, Debrecen, Hungary; 10 Department of Pathology, University of Debrecen, Debrecen, Hungary; 11 Department of Pediatrics, Kenezy Gyula County Hospital, Debrecen, Hungary; 12 Celiac Disease Center, Heim Pal Children’s Hospital, Budapest, Hungary.

aAddress correspondence to this author at: Department of Gastroenterology, University of Debrecen, Nagyerdei krt. 98, H-4032 Debrecen, Hungary. Fax 36-52-314-410; e-mail drpappm{at}yahoo.com.

Background: Haptoglobin (Hp) {alpha}-chain alleles 1 and 2 account for 3 phenotypes that may influence the course of inflammatory diseases via biologically important differences in their antioxidant, scavenging, and immunomodulatory properties. Hp1-1 genotype results in the production of small dimeric, Hp2-1 linear, and Hp2-2 cyclic polymeric haptoglobin molecules. We investigated the haptoglobin polymorphism in patients with celiac disease and its possible association to the presenting symptoms.

Methods: We studied 712 unrelated, biopsy-proven Hungarian celiac patients (357 children, 355 adults; severe malabsorption 32.9%, minor gastrointestinal symptoms 22.8%, iron deficiency anemia 9.4%, dermatitis herpetiformis 15.6%, silent disease 7.2%, other 12.1%) and 384 healthy subjects. We determined haptoglobin phenotypes by gel electrophoresis and assigned corresponding genotypes.

Results: Hp2-1 was associated with a significant risk for celiac disease (P = 0.0006, odds ratio [OR] 1.54, 95% CI 1.20–1.98; prevalence 56.9% in patients vs 46.1% in controls). It was also overrepresented among patients with mild symptoms (69.2%) or silent disease (72.5%). Hp2-2 was less frequent in patients than in controls (P = 0.0023), but patients having this phenotype were at an increased risk for severe malabsorption (OR 2.21, 95% CI 1.60–3.07) and accounted for 45.3% of all malabsorption cases. Celiac and dermatitis herpetiformis patients showed similar haptoglobin phenotype distributions.

Conclusions: The haptoglobin polymorphism is associated with susceptibility to celiac disease and its clinical presentations. The predominant genotype in the celiac population was Hp2-1, but Hp2-2 predisposed to a more severe clinical course. The phenotype-dependent effect of haptoglobin may result from the molecule’s structural and functional properties.




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