Xie G L, Zhang W, Li Z G, Guo D P, Liu C
Department of Pain, Affiliated Tumor Hospital of Zhengzhou University, Zhengzhou 450000, China.
Department of Anesthesiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China.
Zhonghua Yi Xue Za Zhi. 2019 Dec 17;99(47):3720-3724. doi: 10.3760/cma.j.issn.0376-2491.2019.47.009.
To investigate the relationship between single nucleotide polymorphisms of opioid-related genes and high-dose opioid tolerance in patients with cancer pain. Twenty patients (high-dose opioid tolerance group, group A) who were hospitalized in Henan Cancer Hospital from June 2016 to June 2018 and who received high-dose opioid for pain control for more than 1 week were selected as case groups (group A). Thirty patients with stage Ⅳ tumors who were hospitalized in Henan Cancer Hospital and did not have opioid tolerance were randomly selected as the control group (group B). The peripheral blood samples of two groups were taken for DNA extraction. Gene polymorphisms were detected in 15 single nucleotide polymorphisms (SNP) (rs1799971, rs754891060, rs200637194, rs1045642, rs7438135, rs7439366, rs2242480, rs1080985, rs529520, rs581111, rs2234918, rs4680, rs6276, rs3732765, rs9859538) of the nine opioid receptor-related genes (OPRM1,ABCB1,UGT2B7,CYP3A4,CYP2D6,OPRD1, COMT,DRD2,P2RY12) which most likely to affect high-dose opioid tolerance in patients with cancer pain. The distribution of different genotypes of rs7438135 locus in UGT2B7 gene were statistically significant between the two groups (χ(2)=9.68, 0.004). The difference in the distribution of the different genotypes of the rs3732765 locus of the P2RY12 gene in the two groups were at the significant edge (χ(2)=5.57, 0.05). A correlation analysis between the relevant SNP locus and the risk of high-dose opioid tolerance in cancer patients indicated that individuals with rs7438135 GA genotype in cancer patients were at 6.19 times more likely to have high doses of opioid tolerance than individuals with AA genotypes. The rs7438135 locus gene polymorphism of UGT2B7 gene may be a risk predictor for high-dose opioid tolerance. The rs3732765 site of the P2RY12 gene may be a potential predictor of high-dose opioid tolerance.
探讨阿片类相关基因单核苷酸多态性与癌症疼痛患者高剂量阿片类药物耐受性之间的关系。选取2016年6月至2018年6月在河南省肿瘤医院住院、接受高剂量阿片类药物控制疼痛超过1周的患者（高剂量阿片类药物耐受组，A组）作为病例组（A组）。随机选取30例在河南省肿瘤医院住院且无阿片类药物耐受性的Ⅳ期肿瘤患者作为对照组（B组）。采集两组患者的外周血样本进行DNA提取。检测9个阿片受体相关基因（OPRM1、ABCB1、UGT2B7、CYP3A4、CYP2D6、OPRD1、COMT、DRD2、P2RY12）的15个单核苷酸多态性（SNP）（rs1799971、rs754891060、rs200637194、rs1045642、rs7438135、rs7439366、rs2242480、rs1080985、rs529520、rs581111、rs2234918、rs4680、rs6276、rs3732765、rs9859538），这些基因最有可能影响癌症疼痛患者的高剂量阿片类药物耐受性。UGT2B7基因rs7438135位点不同基因型在两组间的分布差异有统计学意义（χ(2)=9.68，P=0.004）。P2RY12基因rs3732765位点不同基因型在两组间的分布差异处于临界值（χ(2)=5.57，P=0.05）。对相关SNP位点与癌症患者高剂量阿片类药物耐受风险的相关性分析表明，癌症患者中rs7438135基因GA基因型个体发生高剂量阿片类药物耐受的可能性是AA基因型个体的6.19倍。UGT2B7基因的rs7438135位点基因多态性可能是高剂量阿片类药物耐受的风险预测指标。P2RY12基因的rs3732765位点可能是高剂量阿片类药物耐受的潜在预测指标。
