| Part OneInvestigation on the ABCB1 and ABCC2polymorphisms and risk of drug-resistant epilepsy in the Inner Mongolia Han populationBackgroud(1)Epilepsy is a common disease in the nervous system,The epilepsy is caused by the brain neurons supersynchronous discharge,and shows sudden,repeatedly and short of the central nervous system dysfunction.Pharmaceutical drug is the main treatment for epilepsy,Its main mechanism is to suppress the excessive discharge of the lesion neurons,or to inhibit the spread of abnormal discharge around the lesion.And some patients showed drug-resistant to antiepileptic drugs.(2)The ATP binding protein family has found that more than fifty,80%ATP binding protein were distributed prokaryotic cells,its four micro area in the structure,two of which was across the hydrophobic membrane micro area,as the important channel of transmembrane transport drugs,the others micro zone was located in the cytoplasmic side of the membrane,and ATP,and provide energy for transport.(3)ABCB1 is also known as P-glycoprotein or multi-drug resistance protein 1,was first found in drug-resistant tumor cells,as energy-dependent membrane proteins,can play the role of efflux pump,can be in the cell of exogenous compounds including drug transport to the extracellular you concentration gradient.Due to the extensive nature of the substrate and distribution,there may be a competitive or non-competitive drug interaction in the combination of drugs,which affects the pharmacokinetic process and changes the clinical curative effect.(4)ABCC2 was also known as resistance associated proteins 2,its main function was restricted within the lumen drugs into cells,limited the drug from the blood into the brain,and liver cells,renal tubular cells and intestinal epithelial cells in drug excretion to nearby lacuna,accelerated drug cleared from tissue.Objective(1)To research ABCB1 rs1045642and rs2032582in the patients with epilepsy drug resistance,which provides a reference for the choice of drug choice for epilepsy patients.(2)To studyABCC2 rs2273697,rs717620in patients with epilepsy drug resistance,single nucleotide gene polymorphism,and providereference for drug selection of epilepsy patients.(3)To provides a theoretical basis for the clinical conclusion of the diagnosis and treatment of patients with epilepsy.Methods(1)254 epilepsy patients were random selected in April,2013-December 2016 to Inner Mongolia medical university affiliated medical,including 104 cases of drug resistant epilepsy,150 cases of epilepsy drug sensitive,through statistical analysis of general clinical characteristics of patients with clinical manifestations,These were deals with the method of PCR-RF patients BCB1 rs1045642,rs2032582andABCC2 rs2273697,rs717620genotype classification,and compared its relevance to the drug-resistant characteristics analysis.Results(1)The mean age of patients with drug-resistant epilepsy and those with drug-responsive epilepsy were 7.60±15.82 and 7.2±16.14,respectively.There are 61(58.65%)males and 43(41.35%)females in patients with drug-resistant epilepsy,and 84(56.00%)males and 66(44.00%)females in those with drug-responsive epilepsy.Compared with patients with drug-responsive epilepsy,patients with drug-resistant epilepsy were more like to be symptomatic epilepsy(x2=22.29,P<0.001).No significant differences were found between the two investigated studies with respect to age(t=0.20,P=0.42),age at first onset(t=1.49,P=0.07),sex(x2=0.18,P=0.67)and type of seizures(x2=3.54,P=0.17).(2)The CC,CT and TT genotypes ofABCC2 rs717620were significant difference between the drug-responsive epilepsy and drug-resistant epilepsy groups(x2=6.01,P=0.04).However,no significant differences were found in the genotype frequencies of ABCB1 rs1045642(x2=1.61,P=0.45)and rs2032582(x2=0.22,P=0.90)andABCC2 rs2273697(x2=0.24,P=0.89)between the two study groups.(3)Using logistic regression analysis,we observed that the TT genotype of ABCB1 rs717620was associated with a higher risk of drug-resistant epilepsy in comparison to the CC genotype(OR=2.97,95%CI=1.11-8.29).In the recessive model,the TT genotype of ABCB1 rs717620was related with an increased risk of drug-resistant epilepsy(OR=2.64,95%CI=1.03-7.13),compared with the CC+CT genotype.However,no significant correlation was found between the ABCB1 rs1045642and rs2032582andABCC2 rs2273697genetic mutations and risk of drug-resistant epilepsy.(4)Moreover,gene-environmental interaction was conducted,and we found that the ABCB1 rs1045642and rs2032582andABCC2 rs2273697and rs717620gene polymorphisms had no interaction with the demographic and clinical variables in the risk of drug-resistant epilepsy.Conclusions(1)No significant differences were found between the two investigated studies with respect to age,sex and type of seizures.(2)The CC,CT and TT genotypes ofABCC2 rs717620were significant difference between the drug-responsive epilepsy and drug-resistant epilepsy groups,no significant differences were found in the genotype frequencies of ABCB1 rs1045642and rs2032582andABCC2 rs2273697.(3)TT genotype of ABCB1 rs717620was associated with a higher risk of drug-resistant epilepsy in comparison to the CC genotype.the ABCB1 rs1045642and rs2032582andABCC2 rs2273697and rs717620gene polymorphisms had no interaction with the demographic and clinical variables in the risk of drug-resistant epilepsy.Part TwoThe Study of Rs-fMRI in drug-resistant epilepsy Patients Using ReHo、ALFF and FC methodsObjectiveEpilepsy is a very common neurological disorder.Although many scholars have done tremendous research in recent years,we still cannot figure out precisely how it occurs and progresses.Brain resting state functional magnetic resonance imaging used to study the spontaneous activity of MRI signals of the blood oxygenation level-dependent(BOLD)of the subjects,on the condition that the subjects are free from the effects of input and output.This examination is more suitable for those diseases that clinically cannot be performed or those that are not involved in patients’ voluntary participating,such as epilepsy,Alzheimer’s disease,schizophrenia,etc.This study was designed to take advantage of blood oxygen level dependent functional magnetic resonance imaging(BOLD-fMRI)to explore the brain function network characteristics of partial epilepsy.MethodsThe resting-state fMRI data of 59 patients with epilepsy and 58 normal volunteers was obtained on a GE 3.0T Signa HDx scanner.We used the methods of regional.homogeneity(ReHo),amplitude of low frequency fluctuation(ALFF)and functional connectivity to analysis the resting state functional MRI data.ResultsAfter the resting-state fMRI data was obtained,35 people are excluded(including 18 patients with epilepsy,17 normal volunteers).A total of 41 right-handed epilepsy patients with partial seizures and a total of 41 right-handed normal controls who are gender-,age-,level of education are matched to patients were recruited to the data processing.1.ReHo:(1)Analysis in the group:In epilepsy patient group and normal control group,the brain regions which the ReHo value increased are mainly located in precuneus,middle frontal gyrus,medial frontal gyrus,precentral gyrus,postcentral gyrus,angular gyrus and cingulate gyrus.These brain regions are mainly located in the default mode network and was distributed bilaterally symmetrical.(2)Analysis between groups:Compared with normal control group,in the resting state,the patients with partial seizures showed statistically significant increased regional homogeneity in Superior frontal gyrus,Middle frontal gyrus,inferior frontal gyrus,middle temporal gyrus,inferior temporal gyrus,corpus callosum,bilateral insula,parietal lobe,precentral gyrus and postcentral gyrus.Regional homogeneity was found to be decreased in supramarginal gyrus,angular gyrus,cuneus,superior temporal gyrus,middle temporal gyrus,occipital lobe,cerebellum,Rectus gyrus.2.ALFF:(1)Analysis in the group:In epilepsy patient group and normal control group,the brain regions which the ALFF value increased are mainly located in middle frontal gyrus,the medial prefrontal gyrus,superior temporal gyrus,postcentral gyrus,angular gyrus,lingual gyrus,precuneus,cingulate gyrus.(2)Analysis between groups:Compared with normal control group,the patients with partial seizures showed statistically significant increased regional homogeneity in Middle frontal gyrus,temporal pole,precentral gyrus,parahippocampal gyrus,caudate nucleus,cingulate gyrus,corpus callosum.ALFF was found to be decreased in medial frontal gyrus,middle frontal gyrus,transverse temporal gyrus,middle temporal gyrus,precuneus,cingulate gyrus,cerebellum.3.Functional connectivity:(1)Analysis in the group:The results of this study proved that the default mode network is not only present in the normal control group which include PCC/precuneus,middle temporal gyrus,MPFC,vACC,inferior parietal lobule,parahippocampal gyrus,but also exist in patients with partial seizures of epilepsy.The scope of brain regions above which includes,temporal gyrus,MPFC,inferior parietal lobule and parahippocampal gyrus in patient group was smaller than control group.(2)Analysis between groups:Compared with normal control group,patients with epilepsy group showed statistically significant increased function connectivity in middle frontal gyrus,superior temporal gyrus,postcentral gyrus,supramarginal gyrus,precuneus,cerebellum posterior lobe,cingulate gyrus,paracentral lobule.Functional connectivity found to be decreased in the middle temporal gyrus,temporal pole,middle frontal gyrus,Caudate nucleus,Parahippocampal gyrus,superior frontal gyrus,postcentral gyrus,the medial prefrontal gyrus in the epilepsy group.ConclusionReHo,ALFF and functional connectivity analysis methods can detect brain BOLD change about abnormal neural activity of epilepsy patients more comprehensively.Therefore,fMRI is a powerful tool to study the pathophysiological mechanisms of epilepsyand may be useful methods to assist in localizing the epileptic foci and evaluating the effect of treatment and prognosis. |
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