UGT1A4基因多态性的种族差异及对拉莫三嗪血药浓度的影响  

Interethnic differences in UGT1A4 genetic polymorphisms and its effect on lamotrigine trough concentrations

作　　者：周亚芳[1] 王雪丁[1] 周列民[2] 张杰[3] 李宏亮[1] 陈子怡[2] 郑洪[1] 戴启麟[2] 黄民[1] 

机构地区：[1]中山大学药学院临床药理研究所,广州510080 [2]中山大学附属第一医院神经内科,广州510080 [3]广东省中医院药学部,广州510080

出　　处：《中国临床药理学杂志》2015年第6期439-442,共4页The Chinese Journal of Clinical Pharmacology

基　　金："十二五"国家科技重大专项资金资助项目(2012ZX09506001-004);国家自然科学基金资助项目(81320108027;81173131;81473283);广东省重点实验室建设基金资助项目(2011A060901014);广东省重大科技专项基金资助项目(2011A080300001)

摘　　要：目的考察UGT1A4 70C〉A、UGT1A4 142T〉G在中国南方人群分布,并与其他种族比较,明确其对拉莫三嗪稳态谷浓度的影响。方法纳入119例中国南方地区单用拉莫三嗪的癫痫患者,用高效液相色谱法测定拉莫三嗪稳态谷浓度,直接测序法对UGT1A4 70C〉A、UGT1A4 142T〉G进行基因分型,比较不同种族间等位基因频率差异,分析不同基因型对拉莫三嗪浓度的影响。结果UGT1A4 70C〉A在中国南方人群中均未发现A等位基因突变,而欧美人群中突变频率为6%-9%。UGT1A4 142T〉G在中国南方人群中突变的G基因频率（26%）显著高于欧美人群（3%-11%）、土耳其人群（13%）及日本人群（13%）（均P〈0.01）。拉莫三嗪稳定剂量,血药浓度以及校正的血药浓度在UGT1A4142T〉G TT组与GT＋GG组中比较差异均无统计学意义（P〉0.05）。结论UGT1A4的种族多态性差异有统计学意义,在中国南方癫痫患者中UGT1A4 142T〉G对拉莫三嗪血药浓度无显著影响。Objective To investigate the distribution of UGT1A4 70 C A and UGT1A4 142 T G in South China population and comparison with other ethnic groups,and also clarify its effect on lamotrigine trough concentrations. Methods 119 unrelated southern China epilepsy patients receiving lamotrigine as monotherapy were included. Steady- state trough concentration of lamotrigine was measured by a high- performance liquid chromatography method. Direct sequencing was applied to clarify the genotypes of UGT1A4 70 C A and UGT1A4 142 T G. Comparisons with the frequencies reported in other ethnic groups and present study were performed. The association between different genotypes and lamotrigine concentration was also been analyzed. Results There is no UGT1A470 C A G allele found in south China population but a high frequency of6%- 9% appeared in western population. The frequency of mutant G allele of UGT1A4 142 T G in Chinese population was significantly higher than the western ethnic groups（ 26% vs. 3%- 11%,P〈 0. 01） and Japanese population（ 26% vs. 13%,P〈 0. 01）. None of stable dose,lamotrigine plasma concentration or dose adjusted concentration was found to significant associate with UGT1A4 142 T G genotypes（ P〈 0. 05）.Conclusion Remarkable interethnic differences exist in UGT1A4 genetic polymorphisms. There is no significant effect of UGT1A4 142 T G on LTG concentrations in southern Chinese patients.

关 键 词：UGT1A4 基因多态性 种族差异 拉莫三嗪 血药浓度 

分 类 号：R968[医药卫生—药理学]