CAJ | 학술논문

目的：探讨UGT2B7 A268G和UGT2B7 G211T基因多态性对丙戊酸血药浓度的影响。方法：用限制性片段长度多态性聚合酶链反应(polymerase chain reaction restriction fragment length polymorphism，PCR-RFLP)的方法分别对248名癫痫患者检测UGT2B7 A268G和UGT2B7 G211T两个位点的基因型，并收集患者的基本流行性病学资料和相关临床信息，如癫痫类型、病史、服药剂量、疗效和肝肾功能等。采用SPSS 13.0软件分别对资料进行多元线性回归、单因素方差分析、卡方检验和配对T检验等方法的数据统计。结果：多元线性回归分析显示，性别、年龄和体质量指数与丙戊酸血药浓度无明显相关，而浓度剂量比率则与血药浓度相关。在被纳入的248名患者中，UGT2B7 A268G和UGT2B7 G211T的基因型均符合哈迪温伯格平衡定律。UGT2B7-268A等位基因频率为30.05%，而G等位基因频率为69.95%，且携带AA，AG，GG不同基因型的患者服用丙戊酸后血药浓度的比较差异有统计学意义(F=5.477， P=0.005)，AA基因组显著高于GG基因组(P=0.048)，其他两组间比较差异无统计学意义(P>0.05). UGT2B7211G等位基因频率为77.24%， T等位基因频率为22.58%；而携带该位点GG，GT和TT不同基因型的患者服用丙戊酸后，三者血药浓度间比较，差异无统计学意义(P>0.05)。结论：本研究揭示了UGT2B7 A268G和UGT2B7 G211T的基因多态在中国汉族癫痫人群中的分布， UGT2B7 A268G基因多态参与体内丙戊酸代谢并进而影响其血药浓度。临床上针对癫痫患者给予丙戊酸药物时，需要考虑患者携带UGT2B7 A268G位所产生的影响而适当调整患者用药剂量。
목적：탐토UGT2B7 A268G화UGT2B7 G211T기인다태성대병무산혈약농도적영향。방법：용한제성편단장도다태성취합매련반응(polymerase chain reaction restriction fragment length polymorphism，PCR-RFLP)적방법분별대248명전간환자검측UGT2B7 A268G화UGT2B7 G211T량개위점적기인형，병수집환자적기본류행성병학자료화상관림상신식，여전간류형、병사、복약제량、료효화간신공능등。채용SPSS 13.0연건분별대자료진행다원선성회귀、단인소방차분석、잡방검험화배대T검험등방법적수거통계。결과：다원선성회귀분석현시，성별、년령화체질량지수여병무산혈약농도무명현상관，이농도제량비솔칙여혈약농도상관。재피납입적248명환자중，UGT2B7 A268G화UGT2B7 G211T적기인형균부합합적온백격평형정률。UGT2B7-268A등위기인빈솔위30.05%，이G등위기인빈솔위69.95%，차휴대AA，AG，GG불동기인형적환자복용병무산후혈약농도적비교차이유통계학의의(F=5.477， P=0.005)，AA기인조현저고우GG기인조(P=0.048)，기타량조간비교차이무통계학의의(P>0.05). UGT2B7211G등위기인빈솔위77.24%， T등위기인빈솔위22.58%；이휴대해위점GG，GT화TT불동기인형적환자복용병무산후，삼자혈약농도간비교，차이무통계학의의(P>0.05)。결론：본연구게시료UGT2B7 A268G화UGT2B7 G211T적기인다태재중국한족전간인군중적분포， UGT2B7 A268G기인다태삼여체내병무산대사병진이영향기혈약농도。림상상침대전간환자급여병무산약물시，수요고필환자휴대UGT2B7 A268G위소산생적영향이괄당조정환자용약제량。
Objective: To investigate the effect of UGT2B7 A268G and UGT2B7 G211T genetic polymorphism on serum drug concentration of valproic acid (VPA). <br> Methods:Genetic polymorphisms of UGT2B7 A268G and UGT2B7 G211T were tested in 248 epileptic patients by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Data including basic information, epilepsy type, times and doses of drug, treatment response and liver and kidney functions were collected. Statistical analysis was performed by SPSS 13.0 through multivariate linear regression, one-way ANOVA,χ2 test, and paired T-test. <br> Results:Based on multivariate linear regression, there was no significant difference between gender, age, or body mass index and VPA, but concentration-to-dose ratios (CDRs) were positively correlated with VPA. hTe genetic polymorphisms of UGT2B7 A268G and UGT2B7 G211T were consistent with Hardy-Weinberg equilibrium. UGT2B7-268A>G allele frequency distribution A was 30.05%, and G was 69.95%. Variance analysis showed that serum drug concentration was significantly different in the genotype of AA, AG, or GG (F=5.477, P=0.005). Further analysis of paired T test showed that AA type was significantly different from GG type (P=0.048), and that serum concentration of AA type was much higher than that of GG type, while no signiifcant difference between AA type and AG type, GG type and AG type. UGT2B7 G211T allele frequency distribution G was 77.24%, and T was 22.58%. hTere was no signiifcant difference in standardized serum concentration among genotypes of GG, GT, and TT. <br> Conclusion:hTis study reveals UGT2B7 A268G genetic polymorphism distribution in Chinese epilepsy population. UGT2B7 A268G plays an important role in VPA’s metabolism, and has certain effect on VPA’s serum concentration. Epilepsy patient with this genotype should be adjusted the dose of VPA to make a therapeutic effect.