Abstract
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. 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 were detected by Spearman's correlations. PD patients exhibited decreased ALFF values in the right inferior occipital gyrus, lingual gyrus, and fusiform gyrus. A significant difference in the interaction of “groups × genotypes” was observed in the right medial frontal gyrus. The ALFF value of the cluster showing significant interactions was positively correlated with HAMD-17 scores (r=0.489, p=0.011) and anhedonia scores (r=0.512, p=0.008) in PD patients with the Ser/Gly or Gly/Gly genotypes. Therefore, D3 gene Ser9Gly polymorphism might be associated with the severity of depression characterized by anhedonia in PD patients.
Highlights
Introduction e characteristic ofParkinson’s disease (PD) neuropathology is a selective loss of dopaminergic neurons in the substantia nigra pars compacta [1], and orally administered levodopa is one of the standard treatments of PD
As dopamine receptors provide vital determinants of dopamine function [2], there is no doubt that polymorphisms in dopamine receptor genes have an effect on PD. ere are five dopamine receptors (DRs) subtypes, of which DR1 and DR5 are composed of D1-like receptors, while DR2, DR3, and DR4 consist of D2-like receptors [3]. e most frequently studied variant point of the dopamine receptor D3 gene (DRD3) is DRD3 Ser9Gly polymorphism [4]
Imaging genetics is an integrated research method which uses neuroimaging and genetics to evaluate the impact of genetic variation on brain function and structure [11], which has been widely used to investigate the effect of gene in several diseases such as PD [12], amnestic mild cognitive impairment [13], and major depressive disorder (MDD) [14]
Summary
Introduction e characteristic ofPD neuropathology is a selective loss of dopaminergic neurons in the substantia nigra pars compacta [1], and orally administered levodopa is one of the standard treatments of PD. The emerging fact demonstrates that DRD3 Ser9Gly polymorphism is closely associated with the clinical manifestations [4,5,6,7,8] and the treatment of PD [9, 10], the results were inconsistent. Intensive studies are needed to explore the role of DRD3 Ser9Gly polymorphism in PD. Imaging genetics is an integrated research method which uses neuroimaging and genetics to evaluate the impact of genetic variation on brain function and structure [11], which has been widely used to investigate the effect of gene in several diseases such as PD [12], amnestic mild cognitive impairment (aMCI) [13], and major depressive disorder (MDD) [14]. Resting-state functional magnetic resonance imaging (rs-fMRI) allows studying spontaneous
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
