[S17.004] Apolipoprotein A1 Levels Are Associated with APOA1 Promoter Variation and Influence Parkinson's Disease Risk
Christine Swanson,1Katherine Li,1Travis Unger,1Michael Gallagher,1Vivianna Van Deerlin,1Pinky Agarwal,2James Leverenz,3John Roberts,3Ali Samii,3Rachel Goldmann Gross,1Howard Hurtig,1Jacqueline Rick,1Daniel Weintraub,1John Trojanowski,1Cyrus Zabetian,3Alice Chen-Plotkin1
1Philadelphia, PA, USA, 2Kirkland, WA, USA, 3Seattle, WA, USA
Objective: Plasma-based biomarkers, coupled with an understanding of their underlying genetic determinants, could lead to new approaches in the treatment of Parkinson's disease (PD). Here, we explore the role of plasma Apolipoprotein (ApoA1) as a risk marker for PD and evaluate the influence of genetic variants on ApoA1 plasma expression.
Background: We previously identified ApoA1 as a candidate biomarker for PD risk, whereby lower ApoA1 levels were associated with earlier age at disease onset. Plasma ApoA1 has been reported to be genetically influenced, with a single nucleotide polymorphism (SNP) rs670 in the promoter region of the APOA1 gene linked with ApoA1 expression. Specifically, the A allele of rs670 has been reported to correlate with higher circulating ApoA1 and HDL levels.
Methods: To evaluate the role of APOA1 promoter variation on ApoA1 expression, we measured plasma ApoA1 and genotyped DNA for rs670. We compared ApoA1 expression among different rs670 genotypes in a discovery cohort (Cohort 1) of 301 PD patients, 80 normal controls, and 165 subjects with other neurodegenerative disease (ND), as well as a replication cohort (Cohort 2) of 158 PD patients. Additionally, rs670 was genotyped in a third cohort of PD and normal controls, and association of genotype with PD across all 3 cohorts was evaluated.
Results: PD patients had lower plasma ApoA1 expression, compared with normal or disease controls (p<0.001). PD patients carrying the GG genotype at rs670 had significantly lower plasma ApoA1 levels compared with PD patients carrying other genotypes (Cohort 1, p=0.009; Cohort 2, p=0.024). Across all three cohorts (1930 PD and 997 normal controls) the rs670 GG genotype showed a trend towards association (p=0.10) with PD.
Conclusions: Our results suggest a model whereby circulating ApoA1 levels act as a biochemical risk factor for the development of PD, with both genetic and other factors influencing ApoA1 expression. Modulation of ApoA1 levels may be a novel therapeutic strategy in PD.
Category - Movement Disorders: Parkinson's Disease
Tuesday, April 29, 2014 4:00 PM
S17: Platform Session: Parkinson's Disease: Genetics and Epidemiology (3:15 PM-5:00 PM)