Objective: To investigate the relationship between the polymorphism of Uridine diphosphate glucuronosyltransferases (UGT)1A4 142T>G (*3, L48V, rs 2011425)and serum concentration of lamotrigine(LTG) in Chinese epileptic patients. Methods: Databases including Cochrane Library, PubMed, Embase, CNKI, VIP and Wanfang were searched for the studies on the relationship of the polymorphisms of UGT1A4 142T>G with concentration of LTG (from the establishment a database to December 1, 2017). Meta-analysis was performed by RevMan 5.3. Results: We pooled data from 6 literatures, including 903 Chinese epileptic patients. Meta-analysis: In terms of the effect of UGT1A4 142T>G polymorphism on the serum concentration/dose ratio(CDR)of LTG, there was no significant difference between the wild-type(TT genotype)group and mutant-type (TG+ GG genotype) group (MD=-0.08, 95% CI (-0.40-0.23)). Further subgroup analysis was performed on LTG monotherapy or valproic acid(VPA)co-administration. For patients treated with LTG as monotherapy, difference was not statistically significant between the 2 groups(MD=0.16, 95% CI(-0.25-0.57)). But in children treated with VPA co-administration, difference was statistically significant between the 2 groups (MD=-0.50, 95% CI(-0.75--0.26)). Conclusion: UGT1A4 142T>G polymorphism has an effect on LTG concentration only with VPA co-administration in Chinese epileptic pediatric patients and those children with wild-type (TT genotype) have a tendency to have a lower serum concentration of lamotrigine.
目的： 评价尿苷二磷酸葡萄糖醛酸转移酶(UGT)1A4 142T>G(*3，L48V，rs 2011425)基因多态性与中国癫痫患者拉莫三嗪(LTG)血药浓度的关系。 方法： 检索Cochrane图书馆、PubMed、Embase、CNKI、维普数据库和万方数据库，查找建库至2017年12月发表的有关UGT 1A4基因多态性与癫痫患者LTG血药浓度关系的文献。应用RevMan5.3软件进行荟萃分析。 结果： 共纳入6篇文献，共计903例中国癫痫患者。荟萃分析结果：UGT1A4 142T>G基因多态性对癫痫患者LTG血药浓度剂量比(CDR)影响，野生型(TT基因型)组与突变型(TG＋GG基因型)组差异无统计学意义[MD＝－0.08，95% CI(－0.40～0.23)]。通过对单药或联合丙戊酸(VPA)用药进一步亚组分析，应用单药治疗的成人及儿童癫痫患者，两组差异无统计学意义[MD＝0.16，95% CI(－0.25～0.57)]；LTG联合VPA治疗的儿童癫痫患者，两组差异有统计学意义[MD＝－0.50，95% CI(－0.75～－0.26)]。 结论： 对于拉莫三嗪联用丙戊酸的中国癫痫患儿，携带UGT1A4 142T>G野生型(TT基因型)的患者拉莫三嗪血药浓度有降低倾向，或对临床治疗产生影响。.
Keywords: Epilepsy; Lamotrigine; Meta-analysis; Polymorphism; UGT1A4.