Association between Parkinson's disease and the HLA-DRB1 locus.: Parkinson's Disease and HLADRB1

Abstract : Two genome-wide association studies (GWASs) recently highlighted the HLA-DRA and HLA-DRB5 genes as associated with Parkinson disease (PD). However, because HLA-DRA displays a low level of polymorphisms and HLA-DRB5 is only present in approximately 20% of the population, these findings are difficult to interpret. Our aims were: (1) to replicate and investigate in greater detail the association between PD and the HLA-DR region; (2) to identify PD-associated HLA alleles; and (3) to perform a meta-analysis of our top finding. As part of 2 French population-based case-control studies of PD including highly ethnically homogeneous participants, we investigated the association between PD and 51 Single-nucleotide polymorphisms (SNPs) in the HLA-DR region. HLA-DRB1 alleles were imputed using the HLA(*) IMP software. HLA typing was performed in a subsample of the participants. We performed a meta-analysis of our top finding based on 4 GWAS data sets. Among 499 cases and 1123 controls, after correction for multiple testing, we found an association with rs660895 (OR/minor allele, 0.70; 95% CI, 0.57-0.87) within the HLA-DRB1 gene, which encodes the most polymorphic HLA-DR chain (DRβ). A meta-analysis (7996 cases, 36455 controls) confirmed this association (OR, 0.86; 95% CI, 0.82-0.91; P < .0001). SNP-based imputation of HLA alleles showed an inverse association between PD and the HLA-DRB1(*) 04 allele. We replicated an association between PD and the HLA-DR region and provided further insight into the loci and alleles involved. The highly polymorphic HLA-DRB1 locus contains rs660895, which represents a more legitimate candidate than previous ones. Our finding is in agreement with the hypothesis of an immune component in PD pathophysiology. © 2012 Movement Disorder Society.
Type de document :
Article dans une revue
Movement Disorders, Wiley, 2012, 27 (9), pp.1104-10. 〈10.1002/mds.25035〉
Liste complète des métadonnées

http://www.hal.inserm.fr/inserm-00721562
Contributeur : Ismaïl Ahmed <>
Soumis le : vendredi 27 juillet 2012 - 18:35:53
Dernière modification le : lundi 8 octobre 2018 - 17:44:04
Document(s) archivé(s) le : vendredi 16 décembre 2016 - 03:23:23

Fichiers

 Accès restreint
Fichier visible le : jamais

Connectez-vous pour demander l'accès au fichier

  •  HLA_2012-0326Rev2Clean.pdf    Visible le : jamais  Fichiers produits par l'(les) auteur(s)
  •  Table2.pdf    Visible le : jamais  Fichiers produits par l'(les) auteur(s)

Identifiants

Collections

Citation

Ismaïl Ahmed, Ryad Tamouza, Marc Delord, Rajagopal Krishnamoorthy, Christophe Tzourio, et al.. Association between Parkinson's disease and the HLA-DRB1 locus.: Parkinson's Disease and HLADRB1. Movement Disorders, Wiley, 2012, 27 (9), pp.1104-10. 〈10.1002/mds.25035〉. 〈inserm-00721562〉

Partager

Métriques

Consultations de la notice

313