The Association Between DRD3 Ser9Gly Polymorphism and Depression Severity in PD

Abstract

Background: More and more evidence suggests that dopamine receptor D3 gene (DRD3) plays an important role in the clinical manifestations and the treatment of Parkinson's disease (PD). DRD3 Ser9Gly polymorphism is the most frequently studied variant point. Our aim was to investigate the potential effect of DRD3 Ser9Gly polymorphism on modulating resting-state brain function and associative clinical manifestations in PD patients. Methods: We consecutively recruited 61 idiopathic PD patients and 47 healthy controls (HC) who were evaluated by clinical scales, genotyped for variant Ser9Gly in DRD3 and underwent resting-state functional magnetic resonance imaging. Based on DRD3 Ser9Gly polymorphism, PD patients and HCs were divided into four subgroups. Then, two-way analysis of covariance (ANCOVA) was applied to investigate main effects and interactions of PD and DRD3 Ser9Gly polymorphism on the brain function via amplitude of low-frequency fluctuations (ALFF) approach. The association between DRD3 Ser9Gly-modulated significantly different brain regions and clinical manifestations was detected by Spearman's correlations. Findings: PD patients exhibited decreased ALFF values in right inferior occipital gyrus, lingual gyrus and fusiform gyrus. A significant difference in the interaction of groups × genotypes was observed in right medial frontal gyrus. The ALFF value of the cluster showing significant interactions was positive correlated with HAMD-17 scores (r=0.489, p=0.011) in PD patients with the Ser/Gly or Gly/Gly genotypes. Interpretation: D3 gene Ser9Gly polymorphism might be associated with depression severity in PD patients. Funding Statement: This work was supported by the National Natural Science Foundation of China (No.81671258), the Science and Technology Project of Jiangsu Provincial Commission of Health and Family Planning (No.H201602), the Natural science foundation of Jiangsu Province (No.BK20141494), the Jiangsu Provincial Personnel Department “the Great of Six Talented Man Peak” Project (No.2014-WSN-013), the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), and the Science and Technology Project of Jiangsu Bureau of Traditional Chinese Medicine (No.YB2015163). Declaration of Interests: The authors declare none. Ethics Approval Statement: This study was approved by the ethics committee of the First Affiliated Hospital of Nanjing Medical University and all participants provided us with written informed consent before participating in the experiment.