A collaborative European search for non-DQA1 *05-DQB1 *02 Celiac disease loci on HLA-Dr3 haplotypes: Analysis of transmission from homozygous parents

Andrew S. Louka, Simon J. Moodie, Kati Karell, Elisabetta Bolognesi, Henry Ascher, Luigi Greco, Patricia Momigliano-Richiardi, Jukka Partanen, Paul J. Ciclitira, Ludvig M. Sollid, P. Holopainen, P. Collin, K. Mustalahti, M. Mäki, F. Clerget-Darpoux, M. C. Babron, F. Clot, J. P. Hugot, S. D'Alfonso, M. GiordanoM. Mellai, I. Coto, S. Percopo, R. Tosi, B. A. Lie, B. Talseth, J. Ek, A. H. Gudjónsdóttir, B. Kristiansson, S. Adamovic, T. Martinsson, L. Samuelsson, Å Torinsson Naluai, J. Wahlström, S. Nilsson, Olle Nerman, J. Fraser, A. King, E. Kondeatis, R. W. Vaughan

Research output: Contribution to journalArticlepeer-review

Abstract

The HLA-DQA1 *05 with DQB1 *02 alleles are a major risk factor for celiac disease (CD). To search for additional human leukocyte antigen (HLA) risk factors, we looked on the DR3-DQ2 risk haplotype, selected because it carries both DQ risk alleles in cis and is the more represented among CD patients. In a European consortium, we identified 109 families with a parent homozygous for DQA1 *05-DQB1 *02. We typed ten microsatellites in the extended HLA complex, and applied the homozygous-parent transmission disequilibrium test (HPTDT) and extended-TDT to transmissions from homozygous parents. These methods eliminate confounding due to linkage disequilibrium between candidate disease loci and the known risk factor DQA1 *05-DQB1 *02, and are favorable when sufficient families are available. We did not find evidence of association with any single market or allele, although weak evidence for additional risk was observed, represented by preferential transmission of six adjacent markers. We tested the largest ever reported HPTDT population in CD, providing unprecedented power. We did not find significant evidence of additional risk-modifying factors on the DR3 haplotype, independent of DQA1 *05-DQB1 *02, although a weak tendency was observed for the B8-DR3 haplotype. This effect should be tested in large populations with significant representations of both B8-DR3 and non-B8 DR3 haplotypes.

Original languageEnglish
Pages (from-to)350-358
Number of pages9
JournalHuman Immunology
Volume64
Issue number3
DOIs
Publication statusPublished - Mar 1 2003

Keywords

  • Celiac disease
  • HLA
  • Homozygous parent TDT
  • Linkage disequilibrium
  • Polymorphism (genetics)

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Fingerprint Dive into the research topics of 'A collaborative European search for non-DQA1 *05-DQB1 *02 Celiac disease loci on HLA-Dr3 haplotypes: Analysis of transmission from homozygous parents'. Together they form a unique fingerprint.

Cite this