目的 探讨尿苷二磷酸葡萄糖醛酸转移酶(UGT)1 A6 rs2070959基因多态性与癫痫患者丙戊酸(VPA)治疗过程中血药浓度的关系.方法 选取本院诊治的癫痫患者200例,收集时间2014年6月至2017年1月,均采用VPA单药治疗,治疗时间≥3个月,患者体内VPA达到稳态,测定患者体内的VPA血药浓度;测定200例癫痫患者的UGT1 A6 rs2070959的基因型、等位基因频率;以高于200例患者体内VPA平均值1倍标准差作为高VPA组、反之作为低VPA组,对比两组患者的一般资料及UGT1 A6 rs2070959的基因型、等位基因频率,分析影响癫痫患者体内VPA血药浓度的因素.结果 高VPA组患者的AA基因型频率77.01％、AG基因型频率18.39％、GG基因型频率4.60％,低VPA组患者的AA基因型频率67.26％、AG基因型频率19.47％、GG基因型频率13.27％,两组比较差异无统计学意义(P＞0.05);高VPA组的等位基因G频率(13.79％)显著低于低VPA组(23.0％),差异有统计学意义(P＜0.05);高VPA组患者的年龄、体重明显大于低VPA组,差异具有统计学意义(P＜0.05);高VPA组患者的性别构成与低VPA组比较,差异无统计学意义(P＞0.05);Logistic回归分析结果显示:癫痫患者的年龄、体重与患者体内VPA浓度呈正相关(P＜0.05),等位基因G表达与癫痫患者体内VPA浓度呈负相关(P＜0.05).结论 UGT1 A6 rs2070959位点等位基因G表达与癫痫患者体内VPA浓度降低有关,突变型患者治疗可能需要更高的VPA剂量.%Objective To investigate the relationship between uridine diphosphate glucuronosyltransferases (UGT) 1A6 rs2070959 polymorphism and serum concentration of valproic acid (VPA) in patients with epilepsy.Methods We selected 200 cases of epilepsy patients treated in our hospital from June 2014-January 2017.All the patients were treated with VPA monotherapy ＞ 3months.When the VPA of patients reached steady state,we detected the VPA blood level.The genotypes and allele frequencies of UGT1A6 rs2070959 in 200 epilepsy patients were determined.The average standard deviation of 1-fold VPA was used as high VPA group and vice versa as low VPA group.The genotype and allele frequencies of UGT1A6 rs2070959 were compared between the two groups,and the influencing factors of VPA concentration in epileptic patients were analyzed.Results The frequencies of A genotype,AG genotype and GG genotype were 77.01％,18.39％ and 4.60％ in the high VPA group,67.26％,19.47％ and 13.27％ in the low VPA group,with no significant difference between the two groups (P ＞ 0.05);the allele G frequency in the high VPA group was significantly lower than that in the low VPA group (13.79％).The age and weight of the high VPA group were significantly higher than those of the low VPA group (P ＜ 0.05),and the gender composition of the high VPA group was not significantly different from that of the low VPA group (P ＞0.05).Logistic regression analysis showed that age and weight gain were positively correlated with VPA concentration (P ＜ 0.05),allele G expression was negatively correlated with VPA concentration (P ＜0.05).Conclusions Allele G expression at UGT1 A6 rs2070959 is associated with decreased VPA concentration in epileptic patients,which may require a higher dose of VPA.
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