Objective: The aim of the present study was to investigate genetic variants in SNCA associated with accelerated deterioration in striatal dopaminergic activity.

Background: Widespread a-synuclein deposition and nigrostriatal dopaminergic degeneration are pathological hallmarks of Parkinson’s disease (PD). Although the precise mechanism is unclear yet, a-synuclein is supposed to have a central role for pathogenesis of PD. Recently, genome wide association studies (GWAS) have shown that genetic variants of SNCA gene is associated with the susceptibility of PD.

Methods: We analyzed 150 PD patients in the Parkinson’s Progressive Markers Initiative (PPMI) cohort. Progressive changes in striatal dopaminergic activity were evaluated calculating annual percentage change of dopamine transporter (DAT) availability in 123I-N-3-fluoropropyl-2-beta-carboxymethoxy-3beta-(4-iodophenyl) nortropane (123I-FP-CIT) single photon emission tomography (SPECT). Annual percentage change (APC) was calculated as follows; [(DAT binding at 12-month follow-up) – (DAT binding at baseline)] / (DAT binding at baseline) * 100(%). We compared the annual percentage changes between genotypes of single nucleotide polymorphisms (SNPs) in the SNCA.

Results: We observed associations 2 SNPs in SNCA with APC of DAT availabilty: i) rs356181 on the caudate nucleus (p = 0.01), and ii) rs3910105 on the caudate nucleus (p = 0.0374) According to post-hoc analyses, TT genotype of rs356181 (vs. CC, p = 0.008), and CC genotype of rs3910105 (vs. TT, p = 0.032) exhibited a more reduction yearly. (Figure and Table)

Conclusions: Our results suggest that genetic variants in SNCA may affect the progression of nigrostriatal dopaminergic degeneration in Parkinson’s disease.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/genetic-variations-of-snca-and-striatal-dopaminergic-dysfunction-in-patients-with-parkinsons-disease/