HLA and Celiac Disease Susceptibility: New Genetic Factors Bring Open Questions about the HLA Influence and Gene-Dosage Effects | Zendy

Luz María Medrano | Zendy; Bárbara Dema | Zendy; Arturo López-Larios | Zendy; Carlos Maluenda | Zendy; Andrés Bodas | Zendy; Natalia LópezPalacios | Zendy; M. Á. Figueredo | Zendy; Miguel FernándezArquero | Zendy; Concepción Núñez | Zendy

Open Access

HLA and Celiac Disease Susceptibility: New Genetic Factors Bring Open Questions about the HLA Influence and Gene-Dosage Effects

Author(s) -

Luz María Medrano,

Bárbara Dema,

Arturo López-Larios,

Carlos Maluenda,

Andrés Bodas,

Natalia LópezPalacios,

M. Á. Figueredo,

Miguel FernándezArquero,

Concepción Núñez

Publication year - 2012

Publication title -

plos one

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 0.99

H-Index - 332

ISSN - 1932-6203

DOI - 10.1371/journal.pone.0048403

Subject(s) - haplotype , genetics , human leukocyte antigen , genotyping , allele , context (archaeology) , biology , genetic predisposition , disease , immunology , genotype , gene , antigen , medicine , paleontology

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.

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