根据年龄组和总药物浓度水平的UGT1A6和UGT2B7相关丙戊酸药物基因组学。
UGT1A6- and UGT2B7-related valproic acid pharmacogenomics according to age groups and total drug concentration levels.
作者信息
Chatzistefanidis Dimitrios, Lazaros Leandros, Giaka Katerina, Nakou Iliada, Tzoufi Meropi, Georgiou Ioannis, Kyritsis Athanassios, Markoula Sofia
机构信息
Department of Neurology, University of Ioannina, Ioannina, Greece.
Medical Genetics & Assisted Reproduction, University of Ioannina, Ioannina, Greece.
出版信息
Pharmacogenomics. 2016 Jun;17(8):827-35. doi: 10.2217/pgs-2016-0014. Epub 2016 May 27.
AIM
The role of UGT1A6 and UGT2B7 polymorphisms and the impact of total drug plasma concentration in valproic acid (VPA) pharmacogenomics.
PATIENTS & METHODS: A total of 134 Greek patients were recruited (76 adults). Patients were genotyped for UGT1A6 19T>G, 541A>G and 552A>C and UGT2B7 802T>C polymorphisms. Patients' demographic and clinical data were registered. Natural logarithm of concentration-to-dose ratio (CDR) was also calculated as the final outcome.
RESULTS
No significant genotype-related differences in VPA metabolism were noted among various subgroups. An increased lnCDR ratio was noted in children patients compared with adults suggesting increased metabolic capability in younger ages.
CONCLUSION
UGT1A6 and UGT2B7 genotypes were not related to significant changes in VPA metabolism, even after controlling for total drug concentration levels. Younger ages were associated with increased VPA clearance rate.
目的
研究尿苷二磷酸葡萄糖醛酸基转移酶1A6（UGT1A6）和尿苷二磷酸葡萄糖醛酸基转移酶2B7（UGT2B7）基因多态性的作用以及总药物血浆浓度在丙戊酸（VPA）药物基因组学中的影响。
患者与方法
共招募了134名希腊患者（76名成年人）。对患者进行UGT1A6基因19T>G、541A>G和552A>C以及UGT2B7基因802T>C多态性的基因分型。记录患者的人口统计学和临床数据。最终结果计算浓度-剂量比（CDR）的自然对数。
结果
各亚组间未观察到VPA代谢存在与基因型相关的显著差异。与成年人相比，儿童患者的lnCDR比值升高，提示年龄较小者代谢能力增强。
结论
即使在控制总药物浓度水平后，UGT1A6和UGT2B7基因型与VPA代谢的显著变化无关。年龄较小与VPA清除率增加有关。
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