Qiu H-B, Zhuang W, Wu T, Xin S, Lin C-Z, Ruan H-L, Zhu X, Huang M, Li J-L, Hou X-Y, Zhou Z-W, Wang X-D
Department of Gastric Surgery, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
Pharmacogenomics J. 2018 May 22;18(3):460-466. doi: 10.1038/tpj.2017.40. Epub 2017 Aug 1.
Imatinib-induced ophthalmological side-effects, including conjunctiva hemorrhage and periorbital oedema, although very common and still remain relatively little understood. The present study investigated the effects of genetic polymorphisms of drug targets and membrane transporters on these side effects. We found that the minor allele of EGFR rs10258429 and SLC22A1 rs683369 were significant risk determinants of conjunctival hemorrhage with OR of 7.061 (95%CI=1.791-27.837, P=0.005 for EGFR rs10258429 CT+TT vs CC), and 4.809 (95%CI=1.267-18.431, P=0.021 for SLC22A1 rs683369 GG+CG vs CC). The minor allele of SLC22A5 rs274558 and ABCB1 rs2235040 were protective factors to periorbital oedema with OR of 0.313 (95%CI=0.149-0.656, P=0.002 for SLC22A5 rs274558 AA+AG vs GG), and 0.253 (95%CI=0.079-0.805, P=0.020 for ABCB1 rs2235040 CT vs CC). These results indicated that variants in EGFR, SLC22A1, SLC22A5 and ABCB1 influenced the incidence of Imatinib-induced ophthalmological toxicities, and polymorphism analyses in associated genes might be beneficial to optimize Imatinib treatment.
伊马替尼引起的眼科副作用，包括结膜出血和眶周水肿，虽然非常常见，但仍了解相对较少。本研究调查了药物靶点和膜转运蛋白的基因多态性对这些副作用的影响。我们发现，表皮生长因子受体（EGFR）rs10258429和溶质载体家族22成员1（SLC22A1）rs683369的次要等位基因是结膜出血的显著风险决定因素，EGFR rs10258429的比值比（OR）为7.061（95%置信区间[CI]=1.791-27.837，EGFR rs10258429 CT+TT与CC相比，P=0.005），SLC22A1 rs683369的OR为4.809（95%CI=1.267-18.431，SLC22A1 rs683369 GG+CG与CC相比，P=0.021）。溶质载体家族22成员5（SLC22A5）rs274558和ATP结合盒转运蛋白B1（ABCB1）rs2235040的次要等位基因是眶周水肿的保护因素，SLC22A5 rs274558的OR为0.313（95%CI=0.149-0.656，SLC22A5 rs274558 AA+AG与GG相比，P=0.002），ABCB1 rs2235040的OR为0.253（95%CI=0.079-0.805，ABCB1 rs2235040 CT与CC相比，P=0.020）。这些结果表明，EGFR、SLC22A1、SLC22A5和ABCB1中的变异影响了伊马替尼引起的眼科毒性的发生率，相关基因的多态性分析可能有助于优化伊马替尼治疗。
