多巴胺D4受体-616位点单核苷酸多态性对原发性夜间遗尿症患儿脑血流量影响的动脉自旋标记成像研究

Effect of DRD4 Receptor 616 C/G Polymorphism on Cerebral Blood Flow in Pediatric Primary Nocturnal Enuresis Patients,A MR Perfusion Imaging Study Using Pulsed Arterial Spin Labeling Technique

目的应用磁共振动脉自旋标记成像（ASL）技术,探讨多巴胺D4受体基因（DRD4）616位点（rs747302）单核苷酸多态性（SNP）对原发性夜间遗尿症（PNE）患儿脑血流量（CBF）的影响。方法前瞻性获取83例PNE患儿及86名正常对照组儿童的CBF数据及DRD4-616位点基因型数据和ASL-MRI扫描资料。采用VBM软件包对CBF数据进行预处理。以年龄、性别作为协变量,以分组（PNE/对照）及基因型（C/G）作为可能的影响因素,进行析因设计的协方差分析。探索分组效应和基因型效应对CBF的影响及分组和基因型之间的交互效应。结果右侧丘脑的CBF受基因型效应影响显著（脑区像素92,F峰值点MNI坐标X=6,Y=-14,Z=10,F_（1,165）=19.85,FDR corrected）。左侧内侧前额叶（m PFC）基因型和分组的交互效应明显（脑区像素138,F峰值点MNI坐标X=-2,Y=-51,Z=8,F_（1,165）=14.59,FDR corrected）。Post-Hoc检验表明携带C等位基因的PNE患儿m PFC的CBF值显著低于G纯合子PNE患儿（t=-4.279,P_（adjusted）〈0.001）。结论DRD4-616 SNP可能通过影响丘脑及m PFC的CBF导致PNE的发病。

Objective To determine whether the 616 C/G single nucleotide polymorphism（SNP）in the dopamine D4receptor（DRD4）promoter rs747302 is associated with abnormal cerebral blood flow（CBF）in children that suffer from primary nocturnal enuresis（PNE）using arterial spin labeling（ASL）methodology.Methods Genomic and ASL imaging data were obtained from 83 PNE pediatric patients and 86 healthy controls.SNP of rs747302 was genotyped.ASL imaging data was collected on a 3.0Tesla MR scanner,CBF data were calculated and post-processed with the VBM8 software package.CBF were compared between different groups（PNE/control）and genotype（C/G）.Results Main effect of genotype in the right thalamus and group genotype interaction in the left medial prefrontal cortex（m PFC）on CBF were found（P0.05,FDR corrected）.Post-hoc testing demonstrated that the C-allele carriers had a significantly decreased CBF compared to the GG homozygotes in the m PFC in the PMNE group（t=-4.279,P_（adjusted）0.001）.Conclusion Among PNE children,C-allele carriers of rs747302 were associated with abnormal CBF in the thalamus and m PFC.