Association of HLA-A and Non-Classical HLA Class I Alleles

Federico Carlini (1, 2) , Virginia Ferreira (2) , Stéphane Buhler (3) , Audrey Tous (1, 2) , Jean-François Eliaou (4) , Céline René (5, 6) , Jacques Chiaroni (1, 2) , Christophe Picard (2, 1) , Julie Di Cristofaro (1, 2)

1 EFS - Alpes-Méditerranée - Etablissement Français du Sang - Alpes-Méditerranée
2 ADES - Anthropologie bio-culturelle, Droit, Ethique et Santé
3 AGP - Laboratoire d'anthropologie, génétique et peuplements
4 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
5 LGMR - Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques
6 Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB)

The HLA-A locus is surrounded by HLA class Ib genes: HLA-E, HLA-H, HLA-G and HLA-F. HLA class Ib molecules are involved in immuno-modulation with a central role for HLA-G and HLA-E, an emerging role for HLA-F and a yet unknown function for HLA-H. Thus, the principal objective of this study was to describe the main allelic associations between HLA-A and HLA-H, -G, -F and -E. Therefore, HLA-A, -E, -G, -H and -F coding polymorphisms, as well as HLA-G UnTranslated Region haplotypes (referred to as HLA-G UTRs), were explored in 191 voluntary blood donors. Allelic frequencies, Global Linkage Disequilibrium (GLD), Linkage Disequilibrium (LD) for specific pairs of alleles and two-loci haplotype frequencies were estimated. We showed that HLA-A, HLA-H, HLA-F, HLA-G and HLA-G UTRs were all in highly significant pairwise GLD, in contrast to HLA-E. Moreover, HLA-A displayed restricted associations with HLA-G UTR and HLA-H. We also confirmed several associations that were previously found to have a negative impact on transplantation outcome. In summary, our results suggest complex functional and clinical implications of the HLA-A genetic region.

Mots clés: Haplotypes; Polymerase chain reaction; Alleles; Untranslated regions; Linkage disequilibrium; Genetic loci; 3' UTR; Renal transplantation

Domaines: Sciences du Vivant [q-bio]; Médecine humaine et pathologie

Federico Carlini, Virginia Ferreira, Stéphane Buhler, Audrey Tous, Jean-François Eliaou, et al.. Association of HLA-A and Non-Classical HLA Class I Alleles. PLoS ONE, 2016, 11 (10), pp.e0163570. ⟨10.1371/journal.pone.0163570⟩. ⟨hal-01447663⟩