颞叶癫痫SCN1A基因rs3812718位点多态性与静息态自发神经活动关系的功能MRI研究

MRI study of association between the SCN1A gene rs3812718 locus polymorphism and spontaneous brain activity in temporal lobe epilepsy

目的采用MR低频振幅(ALFF)分析方法探讨SCN1A基因rs3812718位点多态性对颞叶癫痫患者脑组织自发神经活动的影响。方法回顾性分析2018年3月至2019年8月在解放军联勤保障部队第九〇〇医院癫痫中心就诊的颞叶癫痫患者37例(颞叶癫痫组),另选择与颞叶癫痫组性别、年龄、受教育年限相匹配的28名健康志愿者作为对照组。再依据基因型分为4个亚组,分别为携带风险A等位基因颞叶癫痫亚组(34例,AA/AG-TLE亚组)、携带非风险G等位基因颞叶癫痫亚组(3例,GG-TLE亚组)、携带风险A等位基因对照亚组(20例AA/AG-HC亚组)及携带非风险G等位基因对照亚组(8例,GG-HC亚组)。对被试者进行头颅MR扫描,采用基于MATLAB 2010平台的DPABI软件计算脑区的ALFF值。2组间ALFF值比较采用独立样本t检验;对颞叶癫痫组及对照组的rs3812718位点不同基因型的ALFF值进行多因素方差分析,找出存在交互相应的脑区,然后进行事后简单效应分析。结果颞叶癫痫组左侧边缘叶、左侧海马旁回、左侧梭状回、左侧海马、右侧岛叶及右侧颞叶下回的ALFF值较对照组增高(Alphasim校正P<0.001),左侧额上回、左侧额中回、左侧额下回、右侧额中回、右侧楔前叶、左侧楔前叶、双侧扣带回、右侧角回的ALFF值较对照组减低(Alphasim校正P<0.05)。携带非风险G等位基因受检者的右侧颞叶下回、右侧梭状回、右侧小脑的ALFF值较携带风险A等位基因的受检者增高(t=3.30,Alphasim校正P=0.002)。颞叶癫痫患者的双侧小脑后叶、左侧小脑前叶、左侧颞下回、左侧梭状回、右侧顶上小叶和右侧楔前叶与SCN1Ars3812718基因型存在显著的交互效应;事后简单效应分析表明,与对照组比较,GG-TLE亚组患者左侧小脑后叶、左侧小脑前叶、左侧颞下回及左侧梭状回ALFF值增高(t=5.97,P<0.001),AA/AG-TLE亚组患者右侧顶上小叶、右侧楔前叶及右侧小脑后叶ALFF值减低;相较于GG-TLE亚组,AA/AG-TLE亚组患者左侧小脑后叶、左侧梭状回及左侧颞叶下回ALFF减低。结论SCN1A基因rs3812718位点多态性影响静息状态下自发神经活动,可能是颞叶癫痫的病理生理机制之一。

Objective To investigate the effect of SCN1A gene polymorphism(SCN1A-rs3812718)on the alterations of spontaneous brain activity using amplitude of low-frequency fluctuations(ALFF)of MR in patients with temporal lobe epilepsy(TLE).Methods A total of 37 TLE patients(TLE group)admitted to the Epilepsy Center of the 900th Hospital of Joint Logistic Team from March 2018 to August 2019 were retrospectively analyzed,and another 28 healthy volunteers matched for gender,age,and years of education with the TLE group were selected as the healthy control group(HC group).Sixty-five subjects were divided into four groups by genotype and diagnosis:34 cases in AA/AG-TLE subgroup,3 cases in GG-TLE subgroup,20 cases in AA/AG-HC subgroup and 8 cases in GG-HC subgroup.All subjects underwent sagittal 3D-T1WI and resting-state functional MRI using a Siemens 3.0 T Trio Tim MR scanner.Then ALFF values of the four groups were calculated using DPABI by the MATLAB 2010 platform.The ALFF values between two groups were compared by independent samples t-test.The ALFF values of different genotypes at rs3812718 locus in TLE and HC group were analyzed by multivariate analysis of variance to find out the corresponding brain regions with interaction,and then post hoc simple effect analysis was performed.Results The ALFF values in TLE group significantly increased in left marginal lobe,left parahippocampal gyrus,left fusiform gyrus,left hippocampus,right insular lobe and right inferior temporal gyrus(Alphasim corrected P<0.001)and decreased in the left superior frontal gyrus,left middle frontal gyrus,left inferior frontal gyrus,right middle frontal gyrus,right precuneus,left precuneus,bilateral cingulate gyrus and right angular gyrus(Alphasim correction P<0.05)compared with HC group.Subjects carrying the non-risk G allele had higher ALFF values in the right inferior temporal gyrus,right fusiform gyrus,and right cerebellum than subjects carrying the risk A allele(t=3.30,Alphasim corrected P=0.002).There was a significant interaction effect on posterior cerebellar lobe,left anterior cerebellar lobe,left inferior temporal gyrus,left superior parietal lobule and right precuneus of TLE patients with SCN1A-rs3812718 genotype.Post-hoc simple effect analysis showed that ALFF significantly increased in the left posterior cerebellar lobe,left anterior cerebellar lobe,left inferior temporal gyrus and left fusiform gyrus in GG-TLE subgroup(t=5.97,P<0.001),but significantly decreased in the right superior parietal lobule,right precuneus,right posterior cerebellar lobe in AA/AG-TLE subgroup compared to the HC group.Compared with GG-TLE subgroup,ALFF in left posterior cerebellar lobe,left fusiform gyrus and left inferior temporal gyrus decreased in AA/AG-TLE subgroup.Conclusion SCN1A gene polymorphism in the rs3812718 locus affects spontaneous neural activity in resting state,which may be one of the pathophysiological mechanisms of TLE.