HLA and celiac disease susceptibility: new genetic factors bring open questions about the HLA influence and gene-dosage effects.
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 asso...
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oai:doaj.org-article:718a5ea391c042a9b26e7d3d7dcb427e2021-11-18T08:10:24ZHLA and celiac disease susceptibility: new genetic factors bring open questions about the HLA influence and gene-dosage effects.1932-620310.1371/journal.pone.0048403https://doaj.org/article/718a5ea391c042a9b26e7d3d7dcb427e2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23119005/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Celiac 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.Luz María MedranoBárbara DemaArturo López-LariosCarlos MaluendaAndrés BodasNatalia López-PalaciosM Ángeles FigueredoMiguel Fernández-ArqueroConcepción NúñezPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 10, p e48403 (2012) |
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Medicine R Science Q |
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Medicine R Science Q Luz María Medrano Bárbara Dema Arturo López-Larios Carlos Maluenda Andrés Bodas Natalia López-Palacios M Ángeles Figueredo Miguel Fernández-Arquero Concepción Núñez HLA and celiac disease susceptibility: new genetic factors bring open questions about the HLA influence and gene-dosage effects. |
| description |
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. |
| format |
article |
| author |
Luz María Medrano Bárbara Dema Arturo López-Larios Carlos Maluenda Andrés Bodas Natalia López-Palacios M Ángeles Figueredo Miguel Fernández-Arquero Concepción Núñez |
| author_facet |
Luz María Medrano Bárbara Dema Arturo López-Larios Carlos Maluenda Andrés Bodas Natalia López-Palacios M Ángeles Figueredo Miguel Fernández-Arquero Concepción Núñez |
| author_sort |
Luz María Medrano |
| title |
HLA and celiac disease susceptibility: new genetic factors bring open questions about the HLA influence and gene-dosage effects. |
| title_short |
HLA and celiac disease susceptibility: new genetic factors bring open questions about the HLA influence and gene-dosage effects. |
| title_full |
HLA and celiac disease susceptibility: new genetic factors bring open questions about the HLA influence and gene-dosage effects. |
| title_fullStr |
HLA and celiac disease susceptibility: new genetic factors bring open questions about the HLA influence and gene-dosage effects. |
| title_full_unstemmed |
HLA and celiac disease susceptibility: new genetic factors bring open questions about the HLA influence and gene-dosage effects. |
| title_sort |
hla and celiac disease susceptibility: new genetic factors bring open questions about the hla influence and gene-dosage effects. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/718a5ea391c042a9b26e7d3d7dcb427e |
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