巯嘌呤甲基转移酶基因多态性联合硫鸟嘌呤核苷酸血药浓度监测在硫唑嘌呤治疗炎症性肠病治疗中的临床应用

中国临床药理学与治疗学 ›› 2014, Vol. 19 ›› Issue (3): 302-308.

巯嘌呤甲基转移酶基因多态性联合硫鸟嘌呤核苷酸血药浓度监测在硫唑嘌呤治疗炎症性肠病治疗中的临床应用

夏泉^1,3, 黄燕¹, 汪燕燕¹, 许杜娟¹, 胡乃中², 胡静², 梅俏², 陈飞虎³

¹安徽医科大学第一附属医院药剂科, 合肥 230022,安徽;
²安徽医科大学第一附属医院消化内科, 合肥 230022,安徽;
³安徽医科大学药学院,合肥 230032,安徽

收稿日期:2013-03-19 修回日期:2014-01-16 出版日期:2014-03-26 发布日期:2014-04-10
通讯作者: 许杜娟,女,博士,主任药师,研究方向:临床药理。Tel: 0551-62922442 E-mail: xudujuan6365@163.com
作者简介:夏泉,男,硕士,副主任药师,研究方向:个体化药物治疗。Tel: 0551-62922421 E-mail: xiaquan2010@163.com

Clinical application of monitoring thiopurine methyltransferase gene polymorphism and 6-thioguanine nucleotides concentration in red blood cells on inflammatory bowel disease patients with azathioprine treatment

XIA Quan^1,3, HUANG Yan¹, WANG Yan-yan¹, XU Du-juan¹, HU Nai-zhong², HU Jing², MEI Qiao², CHEN Fei-hu³

¹Department of Pharmacy, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, China;
²Department of Gastroenterology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, China;
³School of Pharmacy, Anhui Medical University, Hefei 230032, Anhui, China

Received:2013-03-19 Revised:2014-01-16 Online:2014-03-26 Published:2014-04-10

摘要/Abstract

摘要： 目的: 探讨巯嘌呤甲基转移酶(TPMT)基因多态性联合红细胞中硫鸟嘌呤核苷酸(6-TGNs)血药浓度监测在硫唑嘌呤治疗炎症性肠病中的临床应用,为实施个体化治疗方案提供参考。方法: 选取临床确诊为炎症性肠病的患者,采用PCR扩增、焦磷酸基因测序法技术检测其TPMT基因第7外显子G460A和第10外显子A719G的2个多态性位点;应用高效液相色谱法测定患者红细胞(RBC)中6-TGNs浓度。结果: 15例患者TPMT^*3基因均为野生型,未发现突变;首次检测的6-TGNs浓度为 147.31～875.26 pmol/L(8×10⁸)RBC,服用相同剂量的患者个体差异较大。结论: TPMT基因多态性检测有助于预测硫唑嘌呤治疗炎症性肠病的骨髓毒副作用,6-TGNs浓度测定有助于药物剂量的调整,两者联合应用可为接受硫唑嘌呤治疗的炎症性肠病患者的个体化治疗提供参考依据。

关键词: 炎症性肠病, 巯嘌呤甲基转移酶基因多态性, 硫鸟嘌呤核苷酸血药浓度, 临床应用

Abstract: AIM: To investigate the clinical application of monitoring TPMT gene polymorphism and 6-TGNs concentration on inflammatory bowel disease (IBD) patients with azathioprine treatment, so as to implementing individual dosage regimen.METHODS: Patients diagnosed with IBD were met the inclusion criteria, the TPMT*3 genotyping assay was based on polymerase chain reaction and Pyrosequencing for TPMT exon 7 (G460A) and TPMT exon 10 (A719G). The concentrations of 6-TGNs in red blood cells were measured by high-performance liquid chromatography.RESULTS: For 15 patients, TPMT^*3 genotyping were wild type and no mutation was found. The initial concentrations of 6-TGNs were 147.31-875.26 pmol per 8×10⁸ RBC and significant individual differences were obvious for patients with same dose azathioprine.CONCLUSION: TPMT genotyping is useful to predict the myelosuppression, while 6-TGNs monitoring is helpful to adjusting dose of azathioprine. Application of combining TPMP genotyping and 6-TGNs monitor may offer a basis for individualized and safe medication for IBD patients.

Key words: inflammatory bowel disease, thiopurine methyltransferase gene polymorphism, 6-TGNs concentration in red blood cells, clinical application

中图分类号:

R969

夏泉, 黄燕, 汪燕燕, 许杜娟, 胡乃中, 胡静, 梅俏, 陈飞虎. 巯嘌呤甲基转移酶基因多态性联合硫鸟嘌呤核苷酸血药浓度监测在硫唑嘌呤治疗炎症性肠病治疗中的临床应用[J]. 中国临床药理学与治疗学, 2014, 19(3): 302-308.

XIA Quan, HUANG Yan, WANG Yan-yan, XU Du-juan, HU Nai-zhong, HU Jing, MEI Qiao, CHEN Fei-hu. Clinical application of monitoring thiopurine methyltransferase gene polymorphism and 6-thioguanine nucleotides concentration in red blood cells on inflammatory bowel disease patients with azathioprine treatment[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(3): 302-308.

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