TY - JOUR
T1 - Human leukocyte antigen variation and Parkinson's disease
AU - Puschmann, Andreas
AU - Verbeeck, Christophe
AU - Heckman, Michael G.
AU - Soto-Ortolaza, Alexandra I.
AU - Lynch, Timothy
AU - Jasinska-Myga, Barbara
AU - Opala, Grzegorz
AU - Krygowska-Wajs, Anna
AU - Barcikowska, Maria
AU - Uitti, Ryan J.
AU - Wszolek, Zbigniew K.
AU - Ross, Owen A.
N1 - Funding Information:
We would like to thank all those who have contributed to our research, particularly the patients and families who donated DNA samples for this work. This work is supported by the family of Carl and Susan Bolch and a Morris K. Udall Parkinson’s Disease Research Center of Excellence ( NINDS P50 #NS072187 ). A. Puschmann received funding from the Swedish Parkinson Academy , AFA Insurance , The Swedish Parkinson Foundation , Apotekare Hedbergs Foundation , Elsa Schmitz Foundation , and Lund University Research Foundation . Z. K. Wszolek is partially supported by the NIH/NINDS 1RC2NS070276, NS057567, P50NS072187 , Mayo Clinic Florida (MCF) Research Committee CR programs ( MCF #90052018 and MCF #90052030 ), and the gift from Carl Edward Bolch, Jr., and Susan Bass Bolch (MCF #90052031/PAU #90052). O. A. Ross is partially supported by the NIH/NINDS P50 #NS072187, 1RC2NS070276 and the American Heart Association .
PY - 2011/6
Y1 - 2011/6
N2 - 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.
AB - 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.
KW - Association studies
KW - Genetics
KW - HLA
KW - HLA-DRA
KW - Human leukocyte antigen
KW - Immune system
KW - Parkinson's disease
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U2 - 10.1016/j.parkreldis.2011.03.008
DO - 10.1016/j.parkreldis.2011.03.008
M3 - Article
C2 - 21482477
AN - SCOPUS:79957935283
SN - 1353-8020
VL - 17
SP - 376
EP - 378
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
IS - 5
ER -