本文選題：癲癇　切入點(diǎn)：丙戊酸鈉　出處：《中南大學(xué)》2014年碩士論文

【摘要】：目的：癲癇目前已有成熟的治療藥物和治療方案,但在約三分之一的患者中抗癲癇藥物療效不佳,患者間療效的差異可能由多個(gè)途徑基因的多態(tài)性造成。丙戊酸鈉作為治療癲癇的常用一線藥物,其臨床療效也存在較大的個(gè)體差異。本研究旨在分析丙戊酸鈉代謝、轉(zhuǎn)運(yùn)和效應(yīng)通路中各相關(guān)基因的多態(tài)性對(duì)于癲癇患者丙戊酸鈉療效的影響。 方法：共入組201名癲癇患者,回訪收集患者一年內(nèi)發(fā)作次數(shù)作為療效的評(píng)判指標(biāo)。其中131名患者對(duì)丙戊酸鈉敏感,另外70名患者耐藥。選擇丙戊酸鈉代謝、轉(zhuǎn)運(yùn)和效應(yīng)通路上的11個(gè)候選基因：ABCB1、CYP2C19、UGT2B7、GRIN2B、SCN1A、SCN2A、GABRA1、 GABRG2.GABRA6.ALDH5A1,ABAT,共24個(gè)SNP。運(yùn)用MALDI-TOFMS法檢測SNP的遺傳變異,并分析各遺傳變異和丙戊酸鈉療效之間的關(guān)系。應(yīng)用logistic回歸分析、t檢驗(yàn)、卡方檢驗(yàn)、多因子降維分析等統(tǒng)計(jì)方法進(jìn)行統(tǒng)計(jì)學(xué)分析。 結(jié)果：24個(gè)SNP等位基因的發(fā)生頻率均符合Hardy-Weinberg平衡。藥物轉(zhuǎn)運(yùn)蛋白,ABATrs1731017CT多態(tài)性與癲癇患者耐藥表型相關(guān)(P=0.048,OR=0.271,95%可信區(qū)間=0.108-0.682)。藥物受體蛋白,SCN2A rs2304016AG多態(tài)性與癲癇患者藥物敏感表型有邊緣顯著相關(guān)性(P=0.09；OR=3.495,95%可信區(qū)間=1.418-8.618)。多因子降維分析顯示最佳基因-基因交互作用組合為ABAT rs1731017同SCN2A rs2304016,有統(tǒng)計(jì)學(xué)意義(P0.0001；OR=3.6892,95%可信區(qū)間=1.9347-7.0347)。 結(jié)論：中國漢族人群癲癇患者中,ABAT rs1731017變異和丙戊酸鈉療效顯著相關(guān),SCN2A rs2304016和丙戊酸鈉療效有邊緣顯著相關(guān)性。ABAT rs1731017和SCN2A rs2304016存在基因-基因交互作用,兩者變異和丙戊酸鈉療效顯著相關(guān)。
[Abstract]:Objective: there are mature drugs and treatments for epilepsy, but antiepileptic drugs are not effective in about 1/3 patients. The difference in efficacy between patients may be caused by polymorphism of multiple pathway genes. Sodium valproate, as a common first-line drug in the treatment of epilepsy, also has significant individual differences in clinical efficacy. The purpose of this study was to analyze the metabolism of sodium valproate. Effects of polymorphisms of genes involved in transport and response pathways on the efficacy of valproate in epileptic patients. Methods: 201 patients with epilepsy were enrolled in the study. The frequency of seizure in one year was collected as the index to evaluate the curative effect. Among them, 131 patients were sensitive to valproate, the other 70 patients were resistant to drugs, and sodium valproate metabolism was selected. Eleven candidate genes: ABCB1, CYP2C19, UGT2B7, GRIN2B, SCN1, GABRG2, GABRG2.GABRA6.ALDH5A1, ABAT24 SNPs were used to detect the genetic variation of SNP, and to analyze the relationship between genetic variation and valproate therapeutic effect. Logistic regression analysis and chi-square test were used to detect the genetic variation of SNP, and to analyze the relationship between the genetic variation and the efficacy of valproate sodium valproate. Statistical methods such as multi-factor dimensionality reduction analysis were analyzed statistically. Results: the frequency of 24 SNP alleles was consistent with the Hardy-Weinberg balance. The polymorphism of drug transporter ABATrs1731017CT was associated with the phenotype of drug resistance in epileptic patients. The multivariate dimensionality reduction analysis showed that the best combination of gene-gene interaction was ABAT rs1731017 and SCN2A rs2304016, with statistical significance of 1.9347-7.0347%. Conclusion: there is a significant correlation between the variation of ABAT rs1731017 and the efficacy of sodium valproate in Chinese Han nationality epilepsy patients. There is a marginal significant correlation between the efficacy of SCN2A rs2304016 and sodium valproate. There is a gene gene interaction between ABAT rs1731017 and SCN2A rs2304016. Both variations were significantly correlated with the efficacy of sodium valproate.
【學(xué)位授予單位】：中南大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R742.1

【共引文獻(xiàn)】

相關(guān)期刊論文 前1條

1 王萍;周伯庭;朱櫻;尹桃;;基因多態(tài)性與癲癇患者卡馬西平耐藥相關(guān)性的Meta分析[J];中國藥房;2014年48期

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本文編號(hào)：1668491