SLC6A3 rs393795基因多态性参与帕金森病异动症的机制研究  

Involvement of SLC6A3 rs393795 Polymorphism in the Mechanism of Levodopa-induced Dyskinesias in Parkinson’s Disease

作　　者：计敏[1] 孙慧敏 甘彩婷 王丽娜 袁永胜[1] 张克忠[1] JI Min;SUN Hui-min;GAN Cai-ting;WANG Li-na;YUAN Yong-sheng;ZHANG Ke-zhong(Department of Neurology,the First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China)

机构地区：[1]南京医科大学第一附属医院神经内科,南京210029

出　　处：《中国临床神经科学》2022年第4期369-376,共8页Chinese Journal of Clinical Neurosciences

基　　金：国家自然科学基金项目(编号:81671258)。

摘　　要：目的 探讨SLC6A3 rs393795基因多态性对帕金森病(PD)患者应用左旋多巴诱发异动症(LID)脑结构及临床特征的影响。方法 纳入PD LID患者39例为LID组,不伴LID(NLID)患者40例为NLID组,健康对照者34例为对照组。3组分别完成临床评估、SLC6A3 rs393795基因多态性分析和MRI检查。根据SLC6A3 rs393795基因多态性测序结果和既往研究结论将3组再各分为2个基因型亚组(对照组:AA=11例,CC/CA=23例;NLID组:AA=13例,CC/CA=27例;LID组:AA=10例,CC/CA=29例)。应用两因素协方差分析LID和SLC 6A 3rs393795基因多态性与脑皮质厚度的相关性,Spearman相关分析差异脑区和临床表现之间的关联。结果 与NLID组比较,LID组患者右额下回眶部皮质厚度相对更厚(F=3.333,P=0.040)。SLC6A3 rs393795基因多态性对LID组双侧楔回皮质厚度有交互作用(左:F=6.253,P=0.003;右:F=5.312,P=0.006);LID组AA型亚组双侧楔回皮质厚度较NLID组AA型亚组降低(左:F=4.548,P=0.013;右:F=2.952,P=0.057)。LID组AA型亚组双侧楔回皮质厚度与统一异动症评定量表(UDysRS)评分呈负相关(左:r=-0.842,P=0.002;右:r=-0.770,P=0.009)。结论 SLC6A3 rs393795基因多态性可能通过影响双侧楔回皮质厚度进而影响PD患者LID症状,AA基因型LID患者楔回皮质厚度下降伴随着LID症状加重。Aim To investigate the potential effect of SLC6A3 rs393795 polymorphism on cortical thickness and relative clinical characteristics in Parkinson’s disease(PD) patients with levodopa-induced dyskinesias(LID).Methods 79 PD and 34 healthy control(HC) participants were recruited to provide clinical,genetic,and functional magnetic resonance imaging data.Then the PD patients were divided into a LID group(n =39) and a NLID group(n =40) in accordance with LID.According to the rs393795 gene sequencing,all subjects were separated into six subgroups:a 10 LID-AA,a 29 LID-CC/CA,a 13 NLIDAA,a 27 NLID-CC/CA,a 11 HC-AA and a 23HC-CC/CA.Main effects and interactions of the groups(LID versus NLID,HC) and the genotypes(AA versus CA/CC) on cortical thickness obtained by Free Surfer were explored using two-way analysis of covariance(ANCOVA) after the controlling age,gender,education and duration.Spearman’s correlations were employed to investigate the relationships between significantly interactive brain regions and clinical manifestations in the subgroups.Results Compared with NLID subjects,LID patients exhibited increased cortical thickness in right orbital part of inferior frontal gyrus(F =3.333,P =0.040).Significant interactions(affected by both disease factor and allelic variation) were detected in bilateral cuneus(left:F =6.253,P =0.003;right:F =5.312,P =0.006).Furthermore,decreased cortical thickness in left cuneus was observed in LID-AA in comparison with NLID-AA(F =4.548,P =0.013).For LID patients with AA genotype,the cortical thickness of bilateral cuneus were negatively correlated with Unified Dyskinesia Rating Scale(UDys RS) score(left:r=-0.842,P =0.002;right:r =-0.770,P =0.009).Conclusion The polymorphism of SLC6A3 rs393795 may affect cortical thickness of bilateral cuneus in LID patients and the decrease of cortical thickness were accompanied by the aggravation of the severity of LID.

关 键 词：帕金森病 异动症 影像遗传学 基因多态性 皮质厚度 

分 类 号：R742.5[医药卫生—神经病学与精神病学]