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HMGB1基因多态性与非小细胞肺癌患者铂类化疗血液学毒性的相关性研究

发表时间:2015-06-15  浏览量:1348  下载量:551
全部作者: 郑艺,尹继业,刘昭前
作者单位: 中南大学湘雅医院临床药理研究所,遗传药理学湖南省重点实验室;湖南省妇幼保健院药学部
摘 要: 目的:探讨高迁移率族蛋白1(high mobility group box 1 protein,HMGB1)基因单核苷酸多态性(single nucleotide polymorphism,SNP)与晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者铂类药物血液学毒性的关系。方法:使用时间飞行质谱生物芯片系统(Sequenom Mass ARRAY)对437例确诊的NSCLC患者HMGB1基因3个标签SNP位点进行分型,讨论其对铂类化疗血液学毒性反应的相关性。结果:未发现HMGB1基因3个SNP位点与铂类总血液学毒性的发生有显著性关联。进一步对各项血液学毒性进行分析时,发现HMGB1 rs1045411突变纯合基因型AA显著增加了患者发生3~4度血小板减少的风险,而rs2249825在显性模型中与3~4度血小板减少显著关联。结论:HMGB1 rs1045411和rs2249825与3~4度血小板减少显著关联,可作为分子标记物预计铂类化疗血液学毒性反应。
关 键 词: 临床药理学;血液学毒性;单核苷酸多态性;高迁移率族蛋白1;铂类;肺癌
Title: Association between HMGB1 genetic variations and hematologic toxicities of platinum-based chemotherapy in NSCLC patients
Author: ZHENG Yi, YIN Jiye, LIU Zhaoqian
Organization: Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Xiangya Hospital, Central South University; Department of Pharmacy, Hunan Provincial Maternal and Child Health Care Hospital
Abstract: Objective: Aimed at discussing the relationship between single nucleotide polymorphism (SNP) in high mobility group box 1 protein (HMGB1) and hematologic toxicity of platinum-based therapy in non-small cell lung cancer (NSCLC) patients. Methods: Sequenom Mass ARRAY was used to detect 3 tagged SNPs in HMGB1 in 437 NSCLC patients as well as their effect on the hematologic toxicity of the platinum-based chemotherapy. Results: No significant correlation is discovered between 3 SNPs in HMGB1 gene with total platimum-based hematologic toxicities. Further analysis of hematologic toxicities revealed that HMGB1 rs1045411 homozygous mutations AA genotype significantly increases the risk of reduction of 3-4 grades thrombocytopenia while rs2249825 is apparently related with the reduction of 3-4 grades thrombocytopenia in dominant model. Conclusion: Polymorphisms of rs1045411 and rs2249825 in HMGB1 are significantly associated with the reduction of 3-4 grades thrombocytopenia, which can be used as molecular marker to predict hematologic toxicity of platinum-based chemotherapy.
Key words: clinical pharmacology; hematologic toxicities; single nucleotide polymorphism; high mobility group box 1 protein; platinum; lung cancer
发表期数: 2015年6月第11期
引用格式: 郑艺,尹继业,刘昭前. HMGB1基因多态性与非小细胞肺癌患者铂类化疗血液学毒性的相关性研究[J]. 中国科技论文在线精品论文,2015,8(11):1157-1163.
 
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