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组织因子和组织因子途径抑制物单核苷酸多态性与肺癌合并静脉血栓栓塞症的相关性

Association of single nucleotide polymorphisms of tissue factor and tissue factor pathway inhibitor with venous thromboembolism in patients with lung cancer

摘要目的 分析组织因子(TF)和组织因子途径抑制物(TFPI)单核苷酸多态性(SNPs)与肺癌合并静脉血栓栓塞症(VTE)的相关性.方法 选取首都医科大学附属北京朝阳医院2009年10月至2013年8月收治的原发非小细胞肺癌(NSCLC)患者152例,其中男105例,女47例,年龄(62.4±13.2)岁;40例合并VTE,112例未合并VTE.选取同期体检中心的79例健康体检者为对照组.留取血标本,提取DNA.采用聚合酶链式反应-限制性片段长多态性的方法检测TF+ 5466A/G、TFPI-287T/C和TFPI-33T/C三个SNPs位点的基因突变情况.采用DNA测序进行验证.结果 肺癌合并VTE组中等位基因TF+ 5466G、TFPI-287C和TFPI-33C的分布频率分别为2.5%、33.8%和8.8%.三个SNPs的基因型和等位基因在肺癌合并VTE组、肺癌未合并VTE组和健康对照组三组间的分布频率差异均无统计学意义(均P >0.05);按照年龄、性别分层,三个SNPs位点的基因型和等位基因分布频率在三组间差异均无统计学意义(均P>0.05).三个SNPs的基因型和等位基因分布频率均与肺癌合并VTE无关(均P>0.05).TF+ 5466A/G、TFPI-287T/C和TFPI-33T/C的基因型和等位基因的分布频率与肺癌合并VTE患者的预后无关(均P>0.05).结论 TT+ 5466A/G、TFPI-287T/C和TFPI-33T/C基因型改变可能与VTE的发生和肺癌患者的预后无关.

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abstractsObjectives To investigate the distributions of single nucleotide polymorphisms (SNPs) of tissue factor (TF) and its inhibitor tissue factor pathway inhibitor (TFPI) and analyze the association of the SNPs with venous thromboembolism (VTE) in lung cancer patients.Methods Between October 2009 and August 2013,a total of 152 hospitalized patients with newly diagnosed primary non-small cell lung cancer were enrolled from Beijing Chao Yang Hospital.Among them [male 105 cases,female 47 cases,with an age of (62.4 ± 13.2) years old],40 cases were lung cancer patients with VTE,112 cases were lung cancer patients without VTE.In the same period,79 healthy controls were included from the physical examination center.All patients' blood specimens were collected and their DNA was isolated.The selected SNPs were TF + 5466A/G,TFPI-287T/C and TFPI-33T/C and they were investigated by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) followed by validation of DNA sequence analysis.Results Allelic frequencies of TF +5466G,TFPI-287C and TFPI-33C were 2.5%,33.8% and 8.8%,respectively.There was no significant difference among the three groups in genotype or allele frequency distributions of TF + 5466A/G,TFPI-287T/C and TFPI-33T/C polymorphisms (all P > 0.05).There was no difference from different genders and ages in allele or genotype frequency distributions of TF +5466A/G,TFPI-287T/C and rTTPI-33T/C polymorphisms among the three groups (all P > 0.05).Meanwhile,the frequency distributions of genotype and allele of the three SNPs were not associated with lung cancer patients with VTE (all P > 0.05).Still,no relationship was found between genotype or allele frequency distributions of the three SNPs with prognosis of lung cancer patients with VTE.Conclusion Genotype alterations in TF + 5466A/G,TFPI-287T/C and TFPI-33T/C may be unrelated to the occurrence of VTE and the prognosis of lung cancer patients with VTE.

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