摘要目的 探讨血管性血友病因子(VWF)基因三个常见变异位点rs216321、rs216325和rs1800378与肺血栓栓塞症(PTE)的相关性.方法 选取2008年11月至2012年3月卫生部北京医院及北京朝阳医院呼吸科确诊的95例PTE患者为PTE组,同期90名健康体检人群为对照组,均采集空腹静脉血,提取基因组DNA.挑选VWF中次要等位基因频率(MAF)＞ 0.05的三个单核苷酸多态性位点:rs216321 (T/C)、rs216325 (G/A)和rs1800378(T/C),经聚合酶链反应(PCR)-Sanger法测序验证,分析两组各位点等位基因及基因型分布频率的差异,并分析其单倍型与PTE的相关性.结果 VWF基因rs216325 (G/A)、rs1800378 (T/C)位点的等位基因频率在两组间的分布差异有统计学意义(P =0.039、0.006);rs216325中AA基因型与PTE的发生正相关(r=1.914,P=0.047),rs1800378中TT基因型与PTE的发生正相关(r=0.282,P=0.008).TGT单倍型在两组间的分布差异有统计学意义,该单倍型与PTE的发生正相关(r=0.239,P＜0.001).结论 VWF基因rs216325及rs1800378位点的变异与PTE具有相关性,其中rs216325中AA基因型携带、rs1800378中TT基因型携带及TGT单倍型携带预示较高的PTE发病风险.

abstractsObjective To elucidate the relationship between three common variation loci of von Willebrand factor (VWF) gene (rs216321,rs216325 and rs1800378) and pulmonary thromboembolism.Methods A total of 95 patients with definite pulmonary thromboembolism (PTE) at Beijing Chaoyang Hospital and Beijing Hospital during November 2008 to March 2012 served as PTE group while 90 healthy subjects at Beijing Hospital during the same period as control group.Fasting venous blood samples were collected for extracting genomic DNA.Three common variation loci with single nucleotide polymorphism were rs216321 (T/C),rs216325 (G/A) and rs1800378 (T/C) and their minor allele frequency was over 0.05 in VWF gene.The method of polymerase chain reaction (PCR)-Sanger was employed for sequencing.The differences of alleleic and genotypic frequencies between PTE and control groups were compared for each locus.And the correlations of their haplotypes with PTE were analyzed.Results The distributions of rs216325 (G/A) and rs1800378 (T/C) in VWF gene had significant difference between PTE and control groups (P =0.039,0.006).And rs216325 with genotype AA was positively correlated with PTE occurrence (r =1.914,P =0.047).And rs1800378 with genotype TT was also positively correlated with PTE occurrence (r =0.282,P =0.008).The distributions of haplotype TGT had significant differences between PTE and control groups.This haplotype was positively correlated with PTE occurrence (r =0.239,P ＜ 0.001).Conclusions The rs216325 and rs1800378 loci variations in VWF gene are associated with PTE,rs216325 with genotype AA and rs1800378 with genotype TT.And haplotype TGT indicates a high risk of PTE onset.