J Clin Neurol.  2019 Jan;15(1):102-107. 10.3988/jcn.2019.15.1.102.

Effect of Single-Nucleotide Polymorphisms on Decline of Dopamine Transporter Availability in Parkinson's Disease

• Shin S
• Kim K
• Lee JM
• Kim EJ
• Kim SJ
• Kim IJ
• Pak K
• Lee MJ

• KMID: 2451152
• DOI: http://doi.org/10.3988/jcn.2019.15.1.102

Abstract

BACKGROUND AND PURPOSE
We aimed to determine the association between the annual changes in dopamine transporter (DAT) availability as measured by 123I-ioflupane (123I-FP-CIT) single-photon-emission computed tomography and single-nucleotide polymorphisms (SNPs) known to be risk factors in Parkinson's disease (PD).
METHODS
In total, 150 PD patients were included from the Parkinson's Progression Markers Initiative database. Specific SNPs that are associated with PD were selected for genotyping. SNPs that were not in Hardy-Weinberg equilibrium or whose minor allele frequency was less than 0.05 were excluded. Twenty-three SNPs met the inclusion criteria for this study. The Kruskal-Wallis test was used to compare annual percentage changes in DAT availability for three subgroups of SNP.
RESULTS
None of the 23 SNPs exerted a statistically significant effect (p < 0.0022) on the decline of DAT availability in PD patients. However, we observed trends of association (p < 0.05) between three SNPs of two genes with the annual percentage change in DAT availability: 1) rs199347 on the putamen (p=0.0138), 2) rs356181 on the caudate nucleus (p=0.0105), and 3) rs3910105 on the caudate nucleus (p=0.0374). A post-hoc analysis revealed that DAT availability was reduced the most for 1) the putamen in the CC genotype of rs199347 (vs. CT, p=0.0199; vs. TT, p=0.0164), 2) the caudate nucleus in the TT genotype of rs356181 (vs. CC, p=0.0081), and 3) the caudate nucleus in the CC genotype of rs3910105 (vs. TT, p=0.0317).
CONCLUSIONS
Significant trends in the associations between three SNPs and decline of DAT availability in PD patients have been discovered.

Keyword

single photon emission computed tomography; ¹²³I-ioflupane; dopamine transporter; single-nucleotide polymorphism; Parkinson's disease

MeSH Terms

Caudate Nucleus
Dopamine Plasma Membrane Transport Proteins*
Dopamine*
Gene Frequency
Genotype
Humans
Parkinson Disease*
Polymorphism, Single Nucleotide
Putamen
Risk Factors
Tomography, Emission-Computed, Single-Photon
Dopamine
Dopamine Plasma Membrane Transport Proteins

Figure

• 

  Fig. 1 Serial changes in the SBR between screening and 12-month follow-up in both the caudate nucleus and putamen (*p<0.0001; data are means with 95% CIs). SBR: specific binding ratio.

• 

  Fig. 2 Effects of single-nucleotide polymorphisms on the annual percentage change in DAT availability: rs199347 on the putamen (A), rs356181 on the caudate nucleus (B), and rs3910105 on the caudate nucleus (C) (*p<0.05, †p<0.01; data are means with 95% CIs). DAT: dopamine transporter.

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