Association of UGT2B7 and ABCB1 genotypes with morphine-induced adverse drug reactions in Japanese patients with cancer
Association of UGT2B7 and ABCB1 genotypes with morphine-induced adverse drug reactions in Japanese patients with cancer
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DOI：
10.1007/s00280-009-1029-2
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发表时间：
2010-01-01
影响因子：
3
通讯作者：
Sasaki, Yasutsuna
中科院分区：
文献类型：
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作者：
Fujita, Ken-ichi;Ando, Yuichi;Sasaki, Yasutsuna
目的：探讨基因多态性对癌症患者吗啡诱导不良事件的影响。我们研究了32例口服硫酸吗啡控释片的日本癌症患者中，与吗啡相关的不良事件与udp -葡萄糖醛酸糖基转移酶（UGT） 2B7、atp结合盒、B亚家族1号（ABCB1）和mu-阿片受体1基因多态性的关系。ABCB1中T/T基因型为1236或TT/TT双倍型为2677和3435与明显较低的疲劳频率（等级1-3）相关（P = 0.012或0.011，Fisher精确检验）。UGT2B7*2基因型与恶心发生率相关（1-3级）（P = 0.023）。未携带UGT2B7*2等位基因的患者恶心发生率高于其他患者。ABCB1的二倍型2677和3435与呕吐频率相关（1-3级）（P = 0.011）。在2677和3435的双倍型中没有GC等位基因的患者没有出现呕吐。我们的研究结果表明，药物遗传学可用于预测吗啡诱导的不良事件的风险。
To investigate the effects of genetic polymorphisms on morphine-induced adverse events in cancer patients.We examined the relation of morphine-related adverse events to polymorphisms in UDP-glucuronosyltransferase (UGT) 2B7, ATP-binding cassette, sub-family B, number 1 (ABCB1), and mu-opioid receptor 1 genes in 32 Japanese cancer patients receiving oral controlled-release morphine sulfate tablets.The T/T genotype at 1236 or TT/TT diplotype at 2677 and 3435 in ABCB1 was associated with significantly lower frequency of fatigue (grades 1-3) (P = 0.012 or 0.011, Fisher's exact test). The UGT2B7*2 genotype was associated with the frequency of nausea (grades 1-3) (P = 0.023). The frequency of nausea was higher in patients without UGT2B7*2 allele than others. The diplotype at 2677 and 3435 in ABCB1 was associated with the frequency of vomiting (grades 1-3) (P = 0.011). No patient whose diplotype was consisted of no GC allele at 2677 and 3435 suffered from vomiting.Our findings suggest that pharmacogenetics can be used to predict the risk of morphine-induced adverse events.