Mbatchi Litaty Céphanoée, Schmitt Antonin, Thomas Fabienne, Cazaubon Yoann, Robert Jacques, Lumbroso Serge, Brouillet Jean-Paul, Pourquier Philippe, Chatelut Etienne, Boyer Jean-Christophe, Evrard Alexandre
Laboratoire de biochimie, Centre Hospitalier Universitaire (CHU) of Nîmes, Hôpital Carémeau, Nîmes, France.
IRCM, Institut de Recherche en Cancérologie de Montpellier, Montpellier, F-34298, INSERM, U1194 France.
Pharmacogenomics. 2015;16(13):1439-50. doi: 10.2217/pgs.15.84. Epub 2015 Aug 12.
The goal of our study was to assess the impact of patients' genetic background on their sensitivity to carboplatin/paclitaxel hematotoxicity.
PATIENTS & METHODS: Parameters describing sensitivity to neutropenia and to thrombocytopenia of 201 patients were extracted from a previous pharmacokinetic/pharmacodynamics analysis, in order to assess their association with 52 candidates SNPs in 18 genes.
Carriers of a T allele of SLCO1B3-rs4149117 were 19% less sensitive to thrombocytopenia than the homozygotes for the G allele (p = 0.00279). Carriers of two copies of the ATG haplotypes of NR1I2-rs1523130, rs3814055 and rs1523127 were 19% less sensitive to thrombocytopenia than those harboring other haplotypes (p = 0.025).
Our results revealed the importance of SLCO1B3 and NR1I2 in the sensitivity to carboplatin/paclitaxel thrombocytopenia.
本研究的目的是评估患者的遗传背景对其对卡铂/紫杉醇血液毒性敏感性的影响。
从先前的药代动力学/药效学分析中提取描述201例患者对中性粒细胞减少和血小板减少敏感性的参数，以评估其与18个基因中52个候选单核苷酸多态性（SNP）的关联。
SLCO1B3基因rs4149117位点T等位基因携带者对血小板减少的敏感性比G等位基因纯合子低19%（p = 0.00279）。NR1I2基因rs1523130、rs3814055和rs1523127位点ATG单倍型两份拷贝的携带者对血小板减少的敏感性比携带其他单倍型的携带者低19%（p = 0.025）。
我们的结果揭示了SLCO1B3和NR1I2在对卡铂/紫杉醇血小板减少敏感性中的重要性。
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