Service interruption on Monday 11 July from 12:30 to 13:00: all the sites of the CCSD (HAL, Epiciences, SciencesConf, AureHAL) will be inaccessible (network hardware connection).
Skip to Main content Skip to Navigation
Journal articles

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.
Document type :
Journal articles
Complete list of metadata

https://www.hal.inserm.fr/inserm-00721562
Contributor : Ismaïl Ahmed Connect in order to contact the contributor
Submitted on : Friday, July 27, 2012 - 6:35:53 PM
Last modification on : Friday, January 7, 2022 - 3:40:06 AM
Long-term archiving on: : Friday, December 16, 2016 - 3:23:23 AM

Files

 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : jamais

Please log in to resquest access to the document

  •  HLA_2012-0326Rev2Clean.pdf    Embargoed until : jamais  Files produced by the author(s)
  •  Table2.pdf    Embargoed until : jamais  Files produced by the author(s)

Identifiers

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⟩

Share

Metrics

Record views

225