中国北方汉族癫痫患者UGT1A4基因分布特点及其多态性与拉莫三嗪血药浓度的关系  

Characteristics of UGT1A4 gene distribution and relationship between its polymorphism and serum concentration of lamotrigine in northern Chinese Han population with epilepsy

作　　者：杨丽亚[1] 林卫红[2] 张晶[1] 常颖[1] 才华[1] 杜巧会 李纯[1] 刘松岩[1] 

机构地区：[1]吉林大学中日联谊医院神经内科,长春130033 [2]吉林大学第一医院神经内科

出　　处：《中华神经科杂志》2015年第3期180-184,共5页Chinese Journal of Neurology

基　　金：吉林省科技发展计划项目（2011743,JF2012c006-13）;吉林大学基本科研业务经费项目（2012211）

摘　　要：目的研究尿苷二磷酸葡萄糖醛酸转移酶（UGT）1A470C〉A（P24T）和142T〉G（IA8V）基因多态性在拉莫三嗪单药治疗的中国北方汉族癫痫患者中的分布特点及UGT1A470C〉A和142T〉G各基因型的突变频率与拉莫三嗪血药浓度的关系。方法收集2011年6月至2012年9月吉林大学第一医院和吉林大学中13联谊医院正规、单一服用拉莫三嗪的癫痫患者106例，应用高效液相色谱串联质谱电喷雾检测法检测拉莫三嗪的血药浓度，应用直接测序法对拉莫三嗪代谢酶UGTIA4P24T和UGT1A4L48V进行基因型分析，并与其他人群的相关研究进行了对比分析。结果所有患者UGT1A4（70C〉A）基因型均为70CC，无突变；而UGT1A4（142T〉G）TT、TG、GG基因型频率分别为77．36％、20．75％、1．89％。UGT1A4142T〉G基因多态性的分布特点与其他亚洲人群（13本、韩国）相比，差异无统计学意义，与白种人相比（约旦、西班牙等），差异有统计学意义。根据UGT1A4（142T〉G）基因型分为A组（142TG＋142GG）和B组（142TY），B组患者的拉莫三嗪标准化血药浓度的平均值[（4．503±1．470）μg／ml]较A组[（2．325±0．599）μg／ml]高，差异有统计学意义（Z=-6．357，P〈0．01）。发现2例UGT1A4127delA基因型患者的拉莫三嗪标准化血药浓度极高，其中1例患者（10．15μg/ml）因出现严重皮疹而停药。结论中国北方汉族癫痫患者UGT1A4基因存在多态性，其中UGT1A4142T〉G、127delA基因多态性可影响拉莫三嗪的血药浓度，是拉莫三嗪血药浓度存在个体差异的重要因素。Objective To investigate the characteristics of UGT1A4 70C 〉 A（P24T） and UGT1 A4 142T 〉 G （L48V） gene distribution and the relationship between their mutation frequency and the serum concentration of lamotrigine in northern Chinese Han population with epilepsy. Methods A total of 106 epileptic patients who took lamotrigine monotherapy from the First Hospital and the China-Japan Union Hospital of Jilin University between June 2011 and September 2012 were recruited. Liquid chromatographytandem mass spectrometry was used to measure the serum concentration of lamotrigine. The genotypes of UGT1A4P24T and UGT1A4L48V in all the patients were determined by direct sequencing, and compared with correlative researches of the rest of the population. Results The genotype of UGT1A4 70C 〉 A of the 106 epilepsy patients was UGT1A4 70CC without mutations. The frequencies of TT, TG and GG genotypes were 77. 36%, 20. 75% and 1.89%, respectively. The distribution characteristics of UGT1A4 142T 〉 G gene polymorphism showed no statistically significant difference compared with other Asian populations （ Japanese, Korean; P 〉 0.05 ）, but with statistically significant difference compared with the whites （ Jordanian, Spaniard, etc ; P 〈 0. 05 ）. According to the genotypes of UGT1A4, the patients were divided into two groups,group A （ 142TG ＋ 142GG） and group B （142TT）. The standardized serum concentration of lamotrigine of group B （ （4. 503 ± 1. 470） μg/ml） was much higher than that of group A （ （2. 325 ±0.599） μg/ml, Z = -6. 357 ,P 〈 0. 01 ）. The standardized serum concentration of lamotrigine in two patients with UGT1A4 127delA genotype was extremely high, one of whom stopped using lamotrigine （ 10. 15 μg/ml） because of skin rashes. Conclusions UGT1 A4 gene has polymorphisms in northern Chinese Han population with epilepsy. UGT1A4 142T 〉 G and 127delA have certain effect on the serum concentration of lamotrigine. The standardized concentrations of lamotrigine in patient

关 键 词：癫痫 葡糖醛酸基转移酶 多态现象 遗传 三嗪类 血药浓度 

分 类 号：R742.1[医药卫生—神经病学与精神病学]