SCN3A基因多态性对丙戊酸钠治疗癫痫疗效的影响

中华行为医学与脑科学杂志 Pub Date : 2020-01-20 DOI:10.3760/CMA.J.CN371468-20190902-00601

Jianmin Huang, Chen Haiyan, Xionglin Tang, H. Ling, Liu Guojun, Yongming Jiang, Ce Gao, Lan-qing Meng

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There was no significant difference in allele and genotype distribution of c. 1441C>T/p.L481L loci between effective group(C, T allele: 47.1%, 52.9%, CC, CT, TT genotype: 23.5%, 47.1%, 29.4%) and ineffective group(C, T allele: 38.8%, 61.2%, CC, CT, TT genotype: 18.7%, 40.3%, 41.0%)(χ2=2.920, P=0.088; χ2=3.099, P=0.212). Compared with the AA + AG genotype, the GG genotype at c. 905A>G/p.N302S locus significantly reduced the efficacy of valproic acid sodium (OR=2.051, 95%CI=1.136-3.703). Compared with genotypes AA+ AG, there were no significant differences in blood concentration of genotype GG of c. 905A>G/p.N302S (t=3.256, P=0.137). Compared with genotypes CC+ CT, there were no significant differences in blood concentration of genotype TT of c. 1441C>T/p.L481L(t=4.628, P=0.082). c.905A>G/p.N302S and c. 1441C>T/p.L481L were without linkage disequilibrium. \n \n \nConclusion \nThese results suggest that the single nucleotide polymorphisms of c. 905A>G/p.N302S in SCN3A genes may play a role in the resistivity of valproic acid sodium in Zhuangzu epilepsies. \n \n \nKey words: \nPolymorphism of SCN3A genes; Zhuangzu epilepsie; Valproic acid sodium; Efficacy","PeriodicalId":9940,"journal":{"name":"中华行为医学与脑科学杂志","volume":"29 1","pages":"61-65"},"PeriodicalIF":0.0000,"publicationDate":"2020-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The influences of SCN3A gene polymorphism on the efficacy of valproic acid sodium in the treatment of epilepsies\",\"authors\":\"Jianmin Huang, Chen Haiyan, Xionglin Tang, H. 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There was no significant difference in allele and genotype distribution of c. 1441C>T/p.L481L loci between effective group(C, T allele: 47.1%, 52.9%, CC, CT, TT genotype: 23.5%, 47.1%, 29.4%) and ineffective group(C, T allele: 38.8%, 61.2%, CC, CT, TT genotype: 18.7%, 40.3%, 41.0%)(χ2=2.920, P=0.088; χ2=3.099, P=0.212). Compared with the AA + AG genotype, the GG genotype at c. 905A>G/p.N302S locus significantly reduced the efficacy of valproic acid sodium (OR=2.051, 95%CI=1.136-3.703). Compared with genotypes AA+ AG, there were no significant differences in blood concentration of genotype GG of c. 905A>G/p.N302S (t=3.256, P=0.137). 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引用次数: 0

摘要

目的探讨SCN3A基因多态性(c.905A>G/p)的影响。N302S和c. 1441C>T/p.L481L)对丙戊酸钠治疗壮族癫痫疗效的影响。方法采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术和直接测序方法，对SCN3A基因c. 905A>G/p进行鉴定。N302S和c. 1441C>T/p。对244例经丙戊酸钠规范化治疗的癫痫患者(有效组85例，无效组139例)进行外周血L481L基因型检测。采用液相色谱-质谱法检测丙戊酸钠血药浓度。评价两组患者基因型及等位基因与丙戊酸钠疗效的相关性，分析不同基因型患者丙戊酸钠血药浓度的差异。c. 905A>G/p的联动不平衡。N302S和c. 1441C>T/p。用SHEsis软件对L481L进行分析。结果c. 905A>G/p的等位基因和基因型分布。有效组(A、G等位基因分别为50.6%、49.4%，AA、AG、GG基因型分别为27.1%、47.1%、25.8%)与无效组(A、G等位基因分别为37.4%、62.6%，AA、AG、GG基因型分别为16.6%、41.7%、41.7%)N302S位点间差异均有统计学意义(χ2=7.501, P=0.006;χ2 = 7.907,P = 0.019)。c. 1441C>T/p的等位基因和基因型分布无显著差异。有效组(C、T等位基因分别为47.1%、52.9%，CC、CT、TT基因型分别为23.5%、47.1%、29.4%)与无效组(C、T等位基因分别为38.8%、61.2%，CC、CT、TT基因型分别为18.7%、40.3%、41.0%)之间的L481L位点差异(χ2=2.920, P=0.088;χ2 = 3.099,P = 0.212)。与AA + AG基因型相比，GG基因型在0.05 ~ 0.05 G/p。N302S位点显著降低丙戊酸钠的疗效(OR=2.051, 95%CI=1.136 ~ 3.703)。与基因型AA+ AG相比，基因型GG的c. 905A>G/p血药浓度无显著差异。(t=3.256, P=0.137)。与CC+ CT基因型比较，TT基因型c. 1441C>T/ P . l481l血药浓度差异无统计学意义(T =4.628, P=0.082)。c.905A > G / p。N302S和c. 1441C>T/p。L481L无连锁不平衡。结论c. 905A>G/p的单核苷酸多态性。SCN3A基因中的N302S可能在壮族癫痫患者丙戊酸钠的电阻率中起作用。关键词:SCN3A基因多态性;Zhuangzu epilepsie;丙戊酸钠;功效

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The influences of SCN3A gene polymorphism on the efficacy of valproic acid sodium in the treatment of epilepsies

Objective To investigate the influences of SCN3A gene polymorphism(c.905A>G/p.N302S and c. 1441C>T/p.L481L) on the efficacy of valproic acid sodium in the treatment of Zhuangzu epilepsies. Methods Using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)technique and the way of direct sequence, the SCN3A gene c. 905A>G/p.N302S and c. 1441C>T/p.L481L genotypes in peripheral blood were detected in 244 epileptic patients (85 cases in effective group and 139 cases of ineffective group) in the standardized treatment of valproic acid sodium.The blood concentration of valproic acid sodium was detected by LC-MS.Evaluating the correlation between the genotype and alleles of two groups of patients and the efficacy of valproic acid sodium and analyzing the difference of valproic acid sodium's blood concentration between different genotypes.The linkage disequilibrium of c. 905A>G/p.N302S and c. 1441C>T/p.L481L were analyzed by software SHEsis. Results The allele and genotype distribution in c. 905A>G/p.N302S loci between effective group(A, G allele: 50.6%, 49.4%, AA, AG, GG genotype: 27.1%, 47.1%, 25.8%) and ineffective group(A, G allele: 37.4%, 62.6%, AA, AG, GG genotype: 16.6%, 41.7%, 41.7%) had statistically significant difference(χ2=7.501, P=0.006; χ2=7.907, P=0.019). There was no significant difference in allele and genotype distribution of c. 1441C>T/p.L481L loci between effective group(C, T allele: 47.1%, 52.9%, CC, CT, TT genotype: 23.5%, 47.1%, 29.4%) and ineffective group(C, T allele: 38.8%, 61.2%, CC, CT, TT genotype: 18.7%, 40.3%, 41.0%)(χ2=2.920, P=0.088; χ2=3.099, P=0.212). Compared with the AA + AG genotype, the GG genotype at c. 905A>G/p.N302S locus significantly reduced the efficacy of valproic acid sodium (OR=2.051, 95%CI=1.136-3.703). Compared with genotypes AA+ AG, there were no significant differences in blood concentration of genotype GG of c. 905A>G/p.N302S (t=3.256, P=0.137). Compared with genotypes CC+ CT, there were no significant differences in blood concentration of genotype TT of c. 1441C>T/p.L481L(t=4.628, P=0.082). c.905A>G/p.N302S and c. 1441C>T/p.L481L were without linkage disequilibrium. Conclusion These results suggest that the single nucleotide polymorphisms of c. 905A>G/p.N302S in SCN3A genes may play a role in the resistivity of valproic acid sodium in Zhuangzu epilepsies. Key words: Polymorphism of SCN3A genes; Zhuangzu epilepsie; Valproic acid sodium; Efficacy

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中华行为医学与脑科学杂志

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期刊介绍： "Chinese Journal of Behavioral Medicine and Brain Science" (CN 37-1468/R, ISSN 1674-6554) is a national academic journal under the supervision of the National Health Commission, sponsored by the Chinese Medical Association and Jining Medical College. The journal was founded in June 1992 and was formerly known as "Chinese Journal of Behavioral Medicine" (1992-1993) and "Chinese Behavioral Medical Science" (1994-2008). In 2009, it was renamed "Chinese Journal of Behavioral Medicine and Brain Science" with the approval of the State Administration of Press, Publication, Radio, Film and Television. The purpose of "Chinese Journal of Behavioral Medicine and Brain Science" is to implement the health and health policies of the Party and the State, implement the principle of combining theory with practice and popularization and improvement, and reflect the major progress in the theory and practical application of behavioral medicine and brain science in my country. It publishes academic papers and scientific research results in the field of behavioral medicine and brain science in my country, and has columns such as monographs/reviews, basic research, clinical research, health prevention, methods and techniques, psychological behavior and evaluation, and systematic evaluation.