亚甲基四氢叶酸还原酶和纤溶酶原激活剂抑制物1基因多态性与结直肠癌术后下肢深静脉血栓形成的关系

Relationship between gene polymorphisms of methylenetetrahydrofolate reductase and plasminogen activator inhibitor-1 and lower limb deep venous thrombosis after colorectal cancer surgery

目的分析亚甲基四氢叶酸还原酶(MTHFR)和纤溶酶原激活剂抑制物1(PAI-1)基因多态性与结直肠癌术后下肢深静脉血栓(DVT)形成的关系。方法回顾性分析2020年2月至2023年2月于张家口市第一医院行手术治疗的100例结直肠癌患者的临床资料,根据术后有无发生下肢DVT分为DVT组20例和非DVT组80例,采用聚合酶链反应方法检测MTHFR基因C677T位点多态性和PAI-1启动子4G/5G基因多态性,采用Logistic回归分析MTHFR基因C677T位点基因多态性和PAI-1启动子4G/5G基因多态性与结直肠癌术后下肢DVT的关系。结果DVT组MTHFR基因C677T位点TT基因频率及T等位基因频率高于非DVT组[65.00%(13/20)比25.00%(20/80)和80.00%(32/40)比38.75%(62/160)],CC基因频率及C等位基因频率低于非DVT组[5.00%(1/20)比47.50%(38/80)和20.00%(8/40)比61.25%(98/160)],差异有统计学意义(P<0.05),两组CT基因频率比较差异无统计学意义(P>0.05);DVT组PAI-1基因4G/4G基因频率及4G等位基因频率高于非DVT组[50.00%(10/20)比21.25%(17/80)和67.50%(27/40)比38.75%(62/160)],5G/5G基因频率及5G等位基因频率低于非DVT组[15.00%(3/20)比43.75%(35/80)和32.50%(13/40)比61.25%(98/160)],差异有统计学意义(P<0.05),两组4G/5G基因频率比较差异无统计学意义(P>0.05);DVT组MTHFR C677T位点TT基因型联合PAI-1启动子4G/4G基因型分布频率高于非DVT组[55.00%(11/20)比22.50%(18/80)],差异有统计学意义(P<0.05)。多因素Logistic回归分析显示,MTHFR C677T位点TT基因型(OR=1.499,95%CI 1.201~1.871)、PAI-1启动子4G/4G基因型(OR=1.471,95%CI 1.170~1.850)及MTHFR C677T位点TT基因型联合PAI-1启动子4G/4G基因型(OR=1.592,95%CI 1.258~2.014)是结直肠癌术后下肢DVT的危险因素(P<0.05)。结论MTHFR C677T位点TT基因型和PAI-1启动子4G/4G基因型与结直肠癌术后下肢DVT形成密切相关,且同时携带有基因型TT型和4G/4G型者发生下肢DVT的风险更高。

Objective To analyze the relationship between gene polymorphisms of methylenetetrahydrofolate reductase(MTHFR)and plasminogen activator inhibitor-1(PAI-1)and lower limb deep venous thrombosis(DVT)after colorectal cancer surgery.Methods The clinical data of patients with colorectal cancer who underwent surgical treatment in Zhangjiakou First Hospital from February 2020 to February 2023 were analyzed retrospectively.According to the presence or absence of lower limb DVT after surgery,the patients were divided into DVT group(20 cases)and non-DVT group(80 cases).The polymorphism of MTHFR C677T and PAI-1 promoter 4G/5G were detected by polymerase chain reaction method.The relationship between the polymorphisms of MTHFR C677T and PAI-1 promoter 4G/5G and lower limb DVT after colorectal cancer surgery was discussed by logistic regression analysis.Results TT genotype frequency and T allele frequency of MTHFR C677T in the DVT group were higher than those in the non-DVT group:65.00%(13/20)vs.25.00%(20/80),80.00%(32/40)vs.38.75%(62/160).CC genotype frequency and C allele frequency were lower than those in the non-DVT group:5.00%(1/20)vs.47.50%(38/80),20.00%(8/40)vs.61.25%(98/160),with statistically significant differences(P<0.05).There was no significant difference in CT genotype frequency between the two groups(P>0.05).4G/4G gene frequency and 4G allele frequency of PAI-1 gene in the DVT group were higher than those in the non-DVT group:50.00%(10/20)vs.21.25%(17/80),67.50%(27/40)vs.38.75%(62/160).5G/5G gene frequency and 5G allele frequency were lower than those in the non-DVT group:15.00%(3/20)vs.43.75%(35/80),32.50%(13/40)vs.61.25%(98/160),with statistically significant differences(P<0.05).There was no significant difference in 4G/5G gene frequency between the two groups(P>0.05).The distribution frequency of TT genotype of MTHFR C677T and 4G/4G genotype of PAI-1 promoter in DVT group was higher than that in non-DVT group:55.00%(11/20)vs.22.50%(18/80),with a statistically significant difference(P<0.05).Multivariate Logistic regression analysis showed that MTHFR C677T TT genotype(OR=1.499,95%CI 1.201 to 1.871),PAI-1 promoter 4G/4G genotype(OR=1.471,95%CI 1.170 to 1.850)and MTHFR The C677T loci TT genotype combined with the 4G/4G genotype of the PAI-1 promoter(OR=1.592,95%CI 1.258 to 2.014)were risk factors for lower limb DVT after colorectal cancer surgery(P<0.05).Conclusions The TT genotype of MTHFR C677T site and the 4G/4G genotype of PAI-1 promoter are closely related to the formation of lower limb DVT after colorectal cancer surgery,and the risk of lower limb DVT is higher in patients with both genotype TT and 4G/4G.