Haptoglobin polymorphism: A novel genetic risk factor for celiac disease development and its clinical manifestations

Maria Papp, Ildiko Foldi, Eva Nemes, Miklos Udvardy, Jolan Harsfalvi, Istvan Altorjay, Istvan Mate, Tamas Dinya, Csaba Varvolgyi, Zsolt Barta, Gabor Veres, Peter Laszlo Lakatos, Judit Tumpek, Laszlo Toth, Erzsebet Szathmari, Aniko Kapitany, Agnes Gyetvai, Ilma R. Korponay-Szabo

Research output: Article

20 Citations (Scopus)


BACKGROUND: Haptoglobin (Hp) α-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.

Original languageEnglish
Pages (from-to)697-704
Number of pages8
JournalClinical chemistry
Issue number4
Publication statusPublished - ápr. 1 2008


ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry, medical

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