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- Title
HLA and Celiac Disease Susceptibility: New Genetic Factors Bring Open Questions about the HLA Influence and Gene-Dosage Effects.
- Authors
Medrano, Luz María; Dema, Bárbara; López-Larios, Arturo; Maluenda, Carlos; Bodas, Andrés; López-Palacios, Natalia; Figueredo, M. Ángeles; Fernández-Arquero, Miguel; Núñez, Concepción; Pietropaolo, Massimo
- Abstract
Celiac disease (CD) is a chronic inflammatory disorder triggered after gluten ingestion in genetically susceptible individuals. The major genetic determinants are HLA-DQA1*05 and HLA-DQB1*02, which encode the DQ2 heterodimer. These alleles are commonly inherited in cis with DRB1*03:01, which is associated with numerous immune-related disorders, in some cases contributing with a different amount of risk depending on the haplotype context. We aimed at investigating those possible differences involving DRB1*03:01-carrying haplotypes in CD susceptibility. A family (274 trios) and a case-control sample (369 CD cases/461 controls) were analyzed. DRB1*03:01-carrying individuals were classified according to the haplotype present (ancestral haplotype (AH) 8.1, AH 18.2 or non-conserved haplotype) after genotyping of HLA-DRB1, -DQA1,-DQB1, - B8, TNF -308, TNF -376 and the TNFa and TNFb microsatellites. We observe that the AH 8.1 confers higher risk than the remaining DRB1*03:01-carrying haplotypes, and this effect only involves individuals possessing a single copy of DQB1*02.CD risk for these individuals is similar to the one conferred by inherit DQA1*05 and DQB1*02 in trans. It seems that an additional CD susceptibility factor is present in the AH 8.1 but not in other DRB1*03:01-carrying haplotypes. This factor could be shared with individuals possessing DQ2.5 trans, according to the similar risk observed in those two groups of individuals.
- Subjects
CELIAC disease; GLUTEN; GENETICS; IMMUNOLOGIC diseases; HAPLOTYPES; MICROSATELLITE repeats
- Publication
PLoS ONE, 2012, Vol 7, Issue 10, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0048403