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

M. Papp, Ildiko Foldi, E. Nemes, M. Udvardy, J. Hársfalvi, I. Altorjay, Istvan Mate, Tamas Dinya, Csaba Varvolgyi, Z. Barta, G. Verès, P. Lakatos, Judit Tumpek, L. Tóth, Erzsebet Szathmari, A. Kapitány, Agnes Gyetvai, Ilma R. Korponay-Szabo

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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
Volume54
Issue number4
DOIs
Publication statusPublished - Apr 1 2008

Fingerprint

Haptoglobins
Celiac Disease
Polymorphism
Phenotype
Dermatitis
Abdomen
Dermatitis Herpetiformis
Genotype
Odds Ratio
Molecules
Iron-Deficiency Anemias
Biopsy
Scavenging
Electrophoresis
Healthy Volunteers
Iron
Antioxidants
Gels
Alleles
Association reactions

ASJC Scopus subject areas

  • Clinical Biochemistry

Cite this

Haptoglobin polymorphism : A novel genetic risk factor for celiac disease development and its clinical manifestations. / Papp, M.; Foldi, Ildiko; Nemes, E.; Udvardy, M.; Hársfalvi, J.; Altorjay, I.; Mate, Istvan; Dinya, Tamas; Varvolgyi, Csaba; Barta, Z.; Verès, G.; Lakatos, P.; Tumpek, Judit; Tóth, L.; Szathmari, Erzsebet; Kapitány, A.; Gyetvai, Agnes; Korponay-Szabo, Ilma R.

In: Clinical Chemistry, Vol. 54, No. 4, 01.04.2008, p. 697-704.

Research output: Contribution to journalArticle

Papp, M. ; Foldi, Ildiko ; Nemes, E. ; Udvardy, M. ; Hársfalvi, J. ; Altorjay, I. ; Mate, Istvan ; Dinya, Tamas ; Varvolgyi, Csaba ; Barta, Z. ; Verès, G. ; Lakatos, P. ; Tumpek, Judit ; Tóth, L. ; Szathmari, Erzsebet ; Kapitány, A. ; Gyetvai, Agnes ; Korponay-Szabo, Ilma R. / Haptoglobin polymorphism : A novel genetic risk factor for celiac disease development and its clinical manifestations. In: Clinical Chemistry. 2008 ; Vol. 54, No. 4. pp. 697-704.
@article{8caa523eaae64783b4c7aaa2644d5adf,
title = "Haptoglobin polymorphism: A novel genetic risk factor for celiac disease development and its clinical manifestations",
abstract = "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.",
author = "M. Papp and Ildiko Foldi and E. Nemes and M. Udvardy and J. H{\'a}rsfalvi and I. Altorjay and Istvan Mate and Tamas Dinya and Csaba Varvolgyi and Z. Barta and G. Ver{\`e}s and P. Lakatos and Judit Tumpek and L. T{\'o}th and Erzsebet Szathmari and A. Kapit{\'a}ny and Agnes Gyetvai and Korponay-Szabo, {Ilma R.}",
year = "2008",
month = "4",
day = "1",
doi = "10.1373/clinchem.2007.098780",
language = "English",
volume = "54",
pages = "697--704",
journal = "Clinical Chemistry",
issn = "0009-9147",
publisher = "American Association for Clinical Chemistry Inc.",
number = "4",

}

TY - JOUR

T1 - Haptoglobin polymorphism

T2 - A novel genetic risk factor for celiac disease development and its clinical manifestations

AU - Papp, M.

AU - Foldi, Ildiko

AU - Nemes, E.

AU - Udvardy, M.

AU - Hársfalvi, J.

AU - Altorjay, I.

AU - Mate, Istvan

AU - Dinya, Tamas

AU - Varvolgyi, Csaba

AU - Barta, Z.

AU - Verès, G.

AU - Lakatos, P.

AU - Tumpek, Judit

AU - Tóth, L.

AU - Szathmari, Erzsebet

AU - Kapitány, A.

AU - Gyetvai, Agnes

AU - Korponay-Szabo, Ilma R.

PY - 2008/4/1

Y1 - 2008/4/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=42449163854&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=42449163854&partnerID=8YFLogxK

U2 - 10.1373/clinchem.2007.098780

DO - 10.1373/clinchem.2007.098780

M3 - Article

C2 - 18258668

AN - SCOPUS:42449163854

VL - 54

SP - 697

EP - 704

JO - Clinical Chemistry

JF - Clinical Chemistry

SN - 0009-9147

IS - 4

ER -