Dataset Information

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

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.

SUBMITTER: Shin S

PROVIDER: S-EPMC6325373 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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

Shin Seunghyeon S Kim Keunyoung K Lee Jae Meen JM Kim Eun Joo EJ Kim Seong Jang SJ Kim In Joo IJ Pak Kyoungjune K Lee Myung Jun MJ

Journal of clinical neurology (Seoul, Korea) 20190101 1

<h4>Background and purpose</h4>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).<h4>Methods</h4>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 ...[more]

PMID: 30618224

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Project description:BackgroundCoffee is the most widely consumed psychostimulant worldwide. Emerging evidence indicates that coffee consumption habit significantly reduces the risk of developing Parkinson's disease (PD). However, the effect of coffee consumption on nigrostriatal dopaminergic neurodegeneration is still largely unknown. We therefore aim to investigate the role of coffee consumption in nigrostriatal dopaminergic neurodegeneration using dopamine transporter (DAT) imaging in PD and healthy controls (HC).MethodsA total of 138 PD patients and 75 HC with questionnaires about coffee consumption, and DAT scans were recruited from the Parkinson's Progression Markers Initiative cohort. Demographic, clinical, and striatal DAT characteristics were compared across subgroups of current, former, and never coffee consumers in PD and HC, respectively. Furthermore, partial correlation analyses were performed to determine whether there was a relationship between coffee cups consumed per day and striatal DAT characteristics in each striatal region. In addition, the factors that may have influenced the loss of nigrostriatal dopaminergic neurons were included in multiple linear regression analyses to identify significant contributing factors to DAT availability in each striatal region.ResultsPD patients had lower DAT availability in each striatal region than HC (p < 0.001). In PD patients, there were significant differences in DAT availability in the caudate (p = 0.008, Bonferroni corrected) across three PD subgroups. Specifically, post hoc tests showed that current coffee consumers had significantly lower DAT availability in the caudate than former coffee consumers (p = 0.01) and never coffee consumers (p = 0.022). In HC, there were significant differences in DAT availability in the caudate (p = 0.031, Bonferroni uncorrected) across three HC subgroups. Specifically, post hoc tests showed that current coffee consumers had significantly lower DAT availability in the caudate than former coffee consumers (p = 0.022). Moreover, correlation analysis revealed that cups per day were negatively correlated with DAT availability in the caudate in current consumers of PD patients (r = - 0.219, p = 0.047). In addition, multiple linear regression analyses showed that current coffee consumption remained an independent predictor of decreased DAT availability in the caudate in PD patients and HC.ConclusionsThis study demonstrates that current coffee consumption is associated with decreased striatal DAT availability in the caudate. However, the effects of caffeine on striatal DAT may fade and disappear after quitting coffee consumption.Trial registrationClinicalTrials.gov, NCT01141023.

Dataset Information

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

Publications

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

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