本文選題：兒童　切入點(diǎn)：耐藥性癲癇　出處：《重慶醫(yī)科大學(xué)》2012年碩士論文　論文類型：學(xué)位論文

【摘要】：第一部分西南地區(qū)兒童CYP3A4基因多態(tài)性分析研究 目的 對(duì)西南地區(qū)兒童CYP3A4~*18A、CYP3A4~*1G基因多態(tài)性進(jìn)行分析，探討其與該地區(qū)癲癇耐藥的相關(guān)性。 方法 應(yīng)用聚合酶鏈反應(yīng)-限制性片段長度多態(tài)性技術(shù)，共檢測238例兒童的CYP3A4~*18A、CYP3A4~*1G基因型頻率和等位基因頻率，其中耐藥性癲癇組兒童（耐藥組）83例、藥物治療有效組兒童（有效組）87例、健康兒童組（正常對(duì)照組）68例。 結(jié)果 （1）CYP3A4~*18A在耐藥組中分布野生純合子93%、突變雜合子7%，等位基因野生型96%、突變型4%；有效組、正常組野生純合子100%，未發(fā)現(xiàn)突變。耐藥組CYP3A4~*18A多態(tài)性的突變雜合子基因型頻率及突變型等位基因頻率高于有效組，差異有顯著意義(P0.05)，耐藥組與正常組基因型頻率及等位基因頻率比較，差異無顯著意義(P0.05)。 （2）CYP3A4~*1G野生純合子在耐藥組、有效組、正常組頻率分別為47%、45%、50%；突變雜合子頻率分別為46%、49%、43%；突變純合子頻率為7%、6%、7%。等位基因野生型頻率分別為70%、70%、71%，突變型頻率分別為30%、30%、29%。3組基因型頻率及等位基因頻率差異均無顯著意義(P0.05)。 結(jié)論 （1）西南地區(qū)兒童CYP3A4~*18A基因多態(tài)性可能與癲癇耐藥存在一定的相關(guān)性，篩查CYP3A4~*18A基因型是指導(dǎo)抗癲癇藥物的選擇，判斷、預(yù)測其治療效果的重要方法之一。 （2）初步研究顯示CYP3A4~*1G基因多態(tài)性與西南地區(qū)兒童癲癇耐藥相關(guān)性不大，更準(zhǔn)確的結(jié)論有待進(jìn)一步擴(kuò)大樣本量來進(jìn)行深入研究。 第二部分CYP3A4基因多態(tài)性與西南地區(qū)兒童耐藥性癲癇相關(guān)性研究 目的 （1）分析83例西南地區(qū)兒童耐藥性癲癇的臨床特征，探討發(fā)生耐藥的可能原因，以便及時(shí)調(diào)整治療方案，改善預(yù)后。 （2）進(jìn)一步研究CYP3A4~*1G在不同發(fā)作類型、不同病因的癲癇兒童中的分布，，探討其與藥物治療效果的相關(guān)性。 方法 收集2010年5月至2011年8月重慶醫(yī)科大學(xué)附屬兒童醫(yī)院神經(jīng)內(nèi)科門診診斷為藥物IE患兒（耐藥組）83例，藥物有效患兒（有效組）87例，采取現(xiàn)場調(diào)查方式收集患兒性別、年齡、首次發(fā)病年齡，發(fā)作形式、發(fā)作次數(shù)，治療情況，神經(jīng)系統(tǒng)發(fā)育情況，腦電圖、影像學(xué)結(jié)果等臨床資料，采用病例對(duì)照分析方法對(duì)耐藥組和有效組臨床資料進(jìn)行比較分析。應(yīng)用聚合酶鏈反應(yīng)-限制性片段長度多態(tài)性技術(shù)檢測兩組患兒CYP3A4~*1G基因多態(tài)性。 結(jié)果 （1）耐藥組與有效組相比，1歲之前發(fā)病率、局灶性和發(fā)作類型無法確定者，有結(jié)構(gòu)性和代謝性病因者，其影像學(xué)異常及腦電圖異常改變幾率明顯增高。 （2）在不同發(fā)作類型的癲癇兒童中CYP3A4~*1G基因型的分布差異無顯著意義(P0.05)。 （3）在遺傳性或者未知病因患兒中，耐藥組突變純合子及突變等位基因頻率明顯高于有效組，差異均有統(tǒng)計(jì)學(xué)意義(P0.05)，在結(jié)構(gòu)性和代謝性病因患兒中，2組基因型及等位基因頻率差異均無顯著意義(P0.05)。 結(jié)論 （1）IE患兒具有如下特點(diǎn)：發(fā)病年齡早，發(fā)作類型以局灶性和無法確定發(fā)作類型為主，病因以結(jié)構(gòu)性和代謝性異常為主，影像學(xué)和腦電圖異常改變多，應(yīng)用兩種及以上的抗癲癇藥物組合者療效差。 （2）CYP3A4~*1G基因型與不同發(fā)作類型的癲癇兒童對(duì)抗癲癇藥物治療反應(yīng)相關(guān)性不明顯。 （3）CYP3A4~*1G突變純合子可能與遺傳性或者未知病因癲癇患兒耐藥具有一定的相關(guān)性。在遺傳性或者未知病因患兒中，篩查CYP3A4~*1G基因型是指導(dǎo)抗癲癇藥物選擇，并判斷、預(yù)測抗癲癇治療效果的重要方法之一。
[Abstract]:Analysis of CYP3A4 gene polymorphism in children in the first part of the southwest region
objective
The polymorphism of CYP3A4~*18A and CYP3A4~*1G gene in the children of Southwest China was analyzed and the correlation with the drug resistance of epilepsy in this area was discussed.
Method
Restriction fragment length polymorphism polymerase chain reaction, were detected in 238 cases of children CYP3A4~*18A, CYP3A4~*1G genotype frequency and allele frequency among drug resistant epilepsy children (resistance group) 83 cases, effective drug treatment group (effective group) 87 cases, healthy children group (normal control group) 68 cases.
Result
(1) the distribution of wild homozygous CYP3A4~*18A in the resistant group 93%, heterozygous mutations in 7% alleles, 96% wild type and mutant 4%; effective group, normal group of wild homozygous 100% mutations were found. Heterozygous genotype frequency resistance group CYP3A4~*18A polymorphism and mutant allele frequency is higher than the effective group, the difference was significant (P0.05) compared with the normal group, group of drug resistant genotype and allele frequencies, no significant difference (P0.05).
(2) CYP3A4~*1G Nobu Juriko in the resistant group, group, normal group frequencies were 47%, 45%, 50%; heterozygote frequencies were 46%, 49%, 43%; homozygote frequency was 7%, 6%, 7%. allele of wild type were 70%, 70%, 71%, mutation frequencies were 30% 30%, 29%.3 group, genotype and allele frequencies were not significant (P0.05).
conclusion
(1) there is a certain correlation between CYP3A4~*18A gene polymorphism and epilepsy drug resistance in Southwest China. Screening CYP3A4~*18A genotype is an important way to guide the selection of antiepileptic drugs, to predict and predict the therapeutic effect.
(2) preliminary studies show that CYP3A4~*1G gene polymorphism is not associated with drug resistance in children in Southwest China. More accurate conclusions need further expansion of sample size for further research.
Study on the relationship between the second part CYP3A4 gene polymorphism and the resistance to epilepsy in children in Southwest China
objective
(1) to analyze the clinical characteristics of 83 cases of drug-resistant epilepsy in the children of Southwest China, and to explore the possible causes of drug resistance in order to adjust the treatment plan in time and improve the prognosis.
(2) to further study the distribution of CYP3A4~*1G in children with different types of seizures and different causes of epilepsy, and to explore the correlation with the effect of drug treatment.
Method
The children's Hospital Affiliated to Medical University Of Chongqing from May 2010 to August 2011 in neurology clinic diagnosed IE patients (drug resistant group) 83 cases, effective in children with drug (effective group) 87 cases, take the field survey collected with gender, age, onset age, seizure type, the number of attacks, treatment, nervous system development, EEG, clinical the results of imaging data, a case-control analysis of drug resistant group and effective group. The clinical data were compared and analyzed. The application of polymerase chain reaction restriction fragment length polymorphism technique was used to detect CYP3A4~*1G gene polymorphism in two groups.
Result
(1) compared with the effective group, the incidence rate of 1 years old group was significantly higher than that of the effective group.
(2) there was no significant difference in the distribution of CYP3A4~*1G genotypes among epileptic children with different types of seizures (P0.05).
(3) in hereditary or unknown etiology in children with homozygous resistant group and mutation allele frequency was significantly higher than the effective group, the differences were statistically significant (P0.05), in patients with structural and metabolic etiology, gene frequency genotype and the differences between the 2 groups was not significant (P0.05).
conclusion
(1) IE children have the following characteristics: the onset age is early, the type of seizure is mainly localized and uncertain, and the main causes are structural and metabolic abnormalities. There are many abnormal changes in imaging and EEG. The combination of two or more antiepileptic drugs has poor efficacy.
(2) the relationship between CYP3A4~*1G genotypes and epileptic children with different types of seizures is not significant.
(3) the homozygous CYP3A4~*1G mutation may have certain correlation with hereditary or unknown etiology in children with epilepsy. Drug resistance in hereditary or unknown etiology in children with screening of CYP3A4~*1G genotype is to guide the selection of anti epileptic drugs, and judge, one of the most important methods to predict anti epilepsy treatment effect.

【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類號(hào)】：R742.1

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