CR1基因多态性对遗忘型轻度认知障碍患者脑功能的影响-东南大学学报医学版

CR1基因多态性对遗忘型轻度认知障碍患者脑功能的影响

单位：1. 东南大学医学院, 江苏南京 210009;
2. 东南大学附属中大医院神经内科, 江苏南京 210009

分类号：R749.1

出版年·卷·期（页码）：2016·35·第五期（692-699）

摘要：

目的：探讨补体受体1（CR1）基因rs3818361多态性对遗忘型轻度认知障碍（aMCI）患者脑功能的影响模式。方法：以85例aMCI患者及135例健康对照（HC）者为研究对象，根据CR1 rs3818361基因型分型，采用静息态功能磁共振成像技术，结合多维度认知神经心理量表评估，运用低频振幅算法，分析CR1 rs3818361多态性对aMCI患者脑功能的影响。结果：（1）多维度认知神经心理量表功能评分在aMCI组和HC组间的差异有统计学意义（P<0.05）。（2）疾病与基因产生交互作用脑区为右侧额上回（rSFG）及前扣带回（AC）。（3）aMCI组GG基因型患者rSFG和AC的低频振幅值与简易精神状态量表评分呈负相关，与连线测试B所耗时间呈正相关（P<0.00238）。结论：CR1 rs3818361基因多态性可影响aMCI患者的总体认知功能和执行功能，且局部脑区活动增强可能是对认知功能障碍的代偿。

Objective: Exploring association of complement receptor 1(CR1) rs3818361 polymorphism with brain resting-state function in amnestic-type mild cognitive impairment(aMCI) patients. Methods: In this study,85 aMCI patients and 135 healthy controls(HC) grouped by their CR1 rs3818361 genotypes underwent resting-state functional magnetic resonance and a clinical interview which focused on neurological and mental status.Gene-brain-behavior relationships were examined to determine the effect of the risk variant on regional brain activity in these subjects. Results: (1) The difference of neurological and mental status between aMCI and HC subjects was significant(P<0.05). (2) Regions of "groups×genotypes" ANOVA interaction were located in right superior frontal gyrus(rSFG) and anterior cingulate(AC). (3) Negative relation of regional brain activity of rSFG and AC with mini-mental state examination(MMSE), positive relation of regional brain activity of rSFG and AC with seconds consumed in trail making test B(TMT-B) were observed in GG carriers of aMCI patients(P<0.002 38). Conclusion: Our findings are the first to show that CR1 rs3818361 polymorphism has a significant influence on overall cognitive function impairment and executive function,which may be compensated by regional brain hyperactivity.

参考文献：

[1] PETERSEN R C,SMITH G E,WARING S C,et al.Mild cognitive impairment:clinical characterization and outcome[J].Arch Neurol,1999,56(3):303-308.
[2] PETERSON R C,ROBERTS R O,KNOPMAN D S,et al.Mild cognitive impairment:ten years later[J].Arch Neurol,2009,66(12):1447-1455.
[3] LAMBERT J C,HEATH S,EVEN G,et al.Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease[J].Nat Genet,2009,41(10):1094-1099.
[4] CARRASQUILLO M M,BELBIN O,HUNTER T A,et al.Replication of CLU,CR1,and PICALM associations with alzheimer disease[J].Arch Neurol,2010,67(8):961-964.
[5] LI Y,SONG D,JIANG Y,et al.CR1 rs3818361 polymorphism contributes to Alzheimer's disease susceptibility in Chinese population[J/OL].Mol Neurobiol,2015(2015-07-21).doi:10.1007/s12035-015-9343-7.
[6] LUO J,LI S,QIN X,et al.Meta-analysis of the association between CR1 polymorphisms and risk of late-onset Alzheimer's disease[J].Neurosci Lett,2014,578(2014):165-170.
[7] MAHMOUDI R,KISSERLI A,NOVELLA J L,et al.Alzheimer's disease is associated with low density of the long CR1 isoform[J].Neurobiol Aging,2015,36(4):1766.e5-1766.e12.
[8] ZHU X C,WANG H F,JIANG T,et al.Effect of CR1 genetic variants on cerebrospinal fluid and neuroimaging biomarkers in healthy,mild cognitive impairment and Alzheimer's disease cohorts[J].Mol Neurobiol,2016(2016-01-07).doi:10.1007/s12035-015-9638-8.
[9] SCHMIDT C,WOLFF M,AHSEN N,et al.CR1 is potentially associated with rate of decline in sporadic Alzheimer's disease[J].J Clin Neurosci,2014,21(10):1705-1708.
[10] BISWAL B,YETKIN F Z,HAUGHTON V M,et al.Functional connectivity in the motor cortex of resting human brain using echo-planar MRI[J].Magn Reson Med,1995,34(4):537-541.
[11] KIVINIEMI V,JAUHIAINEN J,TERVONEN O,et al.Slow vasomotor fluctuation in fMRI of anesthetized child brain[J].Magn Reson Med,2000,44(3):373-378.
[12] ZANG Y F,HE Y,ZHU C Z,et al.Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI[J].Brain Dev,2007,29(2):83-91.
[13] WESTLYE E T,LUNDERVOLD A,ROOTWELT H,et al.Increased hippocampal default mode synchronization during rest in middle-aged and elderly APOE epsilon4 carriers: relationships with memory performance[J].J Neurosci,2011,31(21):7775-7783.
[14] SWEET R A,SELTMAN H,EMANUEL J E,et al.Effect of Alzheimer's disease risk genes on trajectories of cognitive function in the Cardiovascular Health Study[J].Am J Psychiatry,2012,169(9):954-962.
[15] PEDRAZA O,ALLEN M,JENNETTE K,et al.Evaluation of memory endophenotypes for association with CLU,CR1,and PICALM variants in black and white subjects[J].Alzheimers Dement,2014,10(2):205-213.
[16] YETKIN F Z,ROSENBERG R N,WEINER M F,et al.FMRI of working memory in patients with mild cognitive impairment and probable Alzheimer's disease[J].Eur Radiol,2006,16(1):193-206.
[17] BAI F,SHI Y,YUAN Y,et al.Association of a GSK-3beta polymorphism with brain resting-state function in amnestic-type mild cognitive impairment[J].J Alzheimers Dis,2012,32(2):387-396.
[18] LIU X,BAI F,YUE C,et al.The association between TOMM40 gene polymorphism and spontaneous brain activity in amnestic mild cognitive impairment[J].J Neurol,2014,261(8):1499-1507.
[19] GUO Z,LIU X,JIA X,et al.Regional coherence changes in Alzheimer's disease patients with depressive symptoms: a resting-state functional MRI study[J].J Alzheimers Dis,2015,48(3):603-611.
[20] OSHIMA E,TERADA S,SATO S,et al.Frontal assessment battery and brain perfusion imaging in Alzheimer's disease[J].Int Psychogeriatr,2012,24(6):994-1001.
[21] HAROLD D,ABRAHAM R,HOLLINGWORTH P,et al.Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease[J].Nat Genet,2009,41(10):1088-1093.

服务与反馈：

【文章下载】【发表评论】【查看评论】【加入收藏】

提示：您还未登录，请登录！点此登录