期刊
MOVEMENT DISORDERS
卷 27, 期 9, 页码 1104-1110出版社
WILEY-BLACKWELL
DOI: 10.1002/mds.25035
关键词
Parkinson's disease; case-control; genetics; major histocompatibility complex
资金
- INSERM (Institut National de la Sante et de la Recherche Medicale)
- MSA
- Agence Nationale de la Recherche (ANR-Sante-environnement et sante-travail and Maladies neurologiques et maladies psychiatriques)
- Agence Francaise de Securite Sanitaire de l'Environnement et du Travail (AFSSET)
- France Parkinson
- Agence Nationale de la Recherche (ANR)
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 casecontrol 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, 0.570.87) within the HLA-DRB1 gene, which encodes the most polymorphic HLA-DR chain (DR beta). A meta-analysis (7996 cases, 36455 controls) confirmed this association (OR, 0.86; 95% CI, 0.820.91; 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. (c) 2012 Movement Disorder Society
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