title: Human leukocyte antigen variation and Parkinson's disease.
abstract: A role for the immune system in the pathogenesis of Parkinson's Disease (PD) has previously been suggested. A recent genome-wide association (GWA) study identified an association between one single nucleotide polymorphism (SNP) in the human leucocyte antigen (HLA) region (HLA-DRA rs3129882) and PD in a population of American patients with European ancestry. In that study, the minor rs3129882 allele (G) was associated with an increased risk of PD under an additive model. Due to the increased likelihood of obtaining false positive results in GWA studies compared to studies conducted based on a hypothesis-driven approach, repeated validation of findings from GWA studies are necessary. Herein, we evaluated the association between rs3129882 and PD in three different Caucasian patient-control series (combined 1313 patients and 1305 controls) from the US, Ireland, and Poland. We observed no association (OR: 0.96, P = 0.50) between rs3129882 and PD when analyzing our data under an additive or dominant model. In contrast, when examined under a recessive model, the GG genotype was observed to be protective in the Irish (OR: 0.55, P = 0.008), Polish (OR: 0.67, P = 0.040) and combined (OR: 0.75, P = 0.006) patient-control series. In view of these diverging results, the exact role of genetic variation at the HLA region and susceptibility to PD remains to be resolved.
authors.affiliation: Division of Neurogenetics, Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, USA.
authors.forename: Andreas
authors.initials: A
authors.lastname: Puschmann
authors.forename: Christophe
authors.initials: C
authors.lastname: Verbeeck
authors.forename: Michael G
authors.initials: MG
authors.lastname: Heckman
authors.forename: Alexandra I
authors.initials: AI
authors.lastname: Soto-Ortolaza
authors.forename: Timothy
authors.initials: T
authors.lastname: Lynch
authors.forename: Barbara
authors.initials: B
authors.lastname: Jasinska-Myga
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Opala
authors.forename: Anna
authors.initials: A
authors.lastname: Krygowska-Wajs
authors.forename: Maria
authors.initials: M
authors.lastname: Barcikowska
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Uitti
authors.forename: Zbigniew K
authors.initials: ZK
authors.lastname: Wszolek
authors.forename: Owen A
authors.initials: OA
authors.lastname: Ross
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000940:Antigenic Variation / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics*; D059805:HLA-DR alpha-Chains; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D006684:HLA-DR Antigens; D059805:HLA-DR alpha-Chains