Louka Andrew S, Moodie Simon J, Karell Kati, Bolognesi Elisabetta, Ascher Henry, Greco Luigi, Momigliano-Richiardi Patricia, Partanen Jukka, Ciclitira Paul J, Sollid Ludvig M
Institute of Immunology, Rikshospitalet University Hospital, Oslo, Norway.
Hum Immunol. 2003 Mar;64(3):350-8. doi: 10.1016/s0198-8859(02)00822-4.
The HLA-DQA105 with DQB102 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 DQA105-DQB102. 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 DQA105-DQB102, and are favorable when sufficient families are available. We did not find evidence of association with any single marker 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 DQA105-DQB102, 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.
