title: Haptoglobin polymorphism: a novel genetic risk factor for celiac disease development and its clinical manifestations.
abstract: 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.
authors.affiliation: Second Department of Medicine, University of Debrecen, Debrecen, Hungary. drpappm@yahoo.com
authors.forename: Maria
authors.initials: M
authors.lastname: Papp
authors.forename: Ildiko
authors.initials: I
authors.lastname: Foldi
authors.forename: Eva
authors.initials: E
authors.lastname: Nemes
authors.forename: Miklos
authors.initials: M
authors.lastname: Udvardy
authors.forename: Jolan
authors.initials: J
authors.lastname: Harsfalvi
authors.forename: Istvan
authors.initials: I
authors.lastname: Altorjay
authors.forename: Istvan
authors.initials: I
authors.lastname: Mate
authors.forename: Tamas
authors.initials: T
authors.lastname: Dinya
authors.forename: Csaba
authors.initials: C
authors.lastname: Varvolgyi
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Barta
authors.forename: Gabor
authors.initials: G
authors.lastname: Veres
authors.forename: Peter Laszlo
authors.initials: PL
authors.lastname: Lakatos
authors.forename: Judit
authors.initials: J
authors.lastname: Tumpek
authors.forename: Laszlo
authors.initials: L
authors.lastname: Toth
authors.forename: Erzsebet
authors.initials: E
authors.lastname: Szathmari
authors.forename: Aniko
authors.initials: A
authors.lastname: Kapitany
authors.forename: Agnes
authors.initials: A
authors.lastname: Gyetvai
authors.forename: Ilma R
authors.initials: IR
authors.lastname: Korponay-Szabo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002446:Celiac Disease / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006242:Haptoglobins / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: D006242:Haptoglobins