Ross J R, Rutter D, Welsh K, Joel S P, Goller K, Wells A U, Du Bois R, Riley J
Department of Clinical Genomics, Imperial College, London, UK.
Pharmacogenomics J. 2005;5(5):324-36. doi: 10.1038/sj.tpj.6500327.
Morphine is the analgesic of choice for moderate to severe cancer pain; however, 10-30% of patients do not tolerate morphine. This study evaluated genetic variation in the mu-opioid receptor, betaarrestin2, stat6 and uridine diphosphate-glucuronysltransferase 2B7 (UGT2B7) genes, in patients who responded to morphine vs those who were switched to alternative opioids. We prospectively recruited and genotyped 162 Caucasian patients (117 controls, 39 switchers). Switchers, were more likely to carry the common allele at 1182 G/A, 5864 G/A, 8622T/C and 11143 G/A in the betaarrestin2 gene (P = 0.021, 0.043, 0.013, 0.043, respectively). Switchers had increased carriage of the T allele (-1714 C/T) and a significant difference in the allelic frequency at 9065 C/T (chi(2) = 3.86, P = 0.049) in the stat6 gene. No differences were seen in genotype or allele frequencies of SNPs in the mu-opioid receptor gene or UGT2B7 gene. This study presents novel data suggesting that variation in genes involved in mu-opioid receptor signalling influence clinical response to morphine.
吗啡是治疗中度至重度癌痛的首选镇痛药；然而，10%至30%的患者不耐受吗啡。本研究评估了对吗啡有反应的患者与改用其他阿片类药物的患者在μ-阿片受体、β-抑制蛋白2、信号转导和转录激活因子6（Stat6）以及尿苷二磷酸葡萄糖醛酸基转移酶2B7（UGT2B7）基因上的基因变异情况。我们前瞻性招募了162名白种人患者（117名对照者，39名改用其他药物者）并进行基因分型。改用其他药物者更有可能在β-抑制蛋白2基因的1182G/A、5864G/A、8622T/C和11143G/A位点携带常见等位基因（P值分别为0.021、0.043、0.013、0.043）。改用其他药物者Stat6基因的T等位基因（-1714C/T）携带率增加，且在9065C/T位点的等位基因频率存在显著差异（χ2 = 3.86，P = 0.049）。在μ-阿片受体基因或UGT2B7基因的单核苷酸多态性（SNP）的基因型或等位基因频率方面未发现差异。本研究提供了新的数据，表明参与μ-阿片受体信号传导的基因变异会影响对吗啡的临床反应。
