Haptoglobin polymorphism: a novel genetic risk factor for celiac disease development and its clinical manifestations.
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.
Papp
Maria
M
Second Department of Medicine, University of Debrecen, Debrecen, Hungary. drpappm@yahoo.com
Foldi
Ildiko
I
Nemes
Eva
E
Udvardy
Miklos
M
Harsfalvi
Jolan
J
Altorjay
Istvan
I
Mate
Istvan
I
Dinya
Tamas
T
Varvolgyi
Csaba
C
Barta
Zsolt
Z
Veres
Gabor
G
Lakatos
Peter Laszlo
PL
Tumpek
Judit
J
Toth
Laszlo
L
Szathmari
Erzsebet
E
Kapitany
Aniko
A
Gyetvai
Agnes
A
Korponay-Szabo
Ilma R
IR
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
D006242:Haptoglobins