VEGF基因多态性与薄型子宫内膜关系探究

Relationship between VEGF gene polymorphism and thin endometrium

目的 研究血管内皮生长因子(VEGF)基因启动子区-2578C/A、-1154G/A、-460C/T、+936C/T多态性位点与薄型子宫内膜的关系。方法 选取2023年1~12月于衡水市第四人民医院妇科门诊就诊或住院的100例薄型子宫内膜患者为研究组,同期体检的100例健康成年女性为对照组。检测两组血清VEGF水平、子宫内膜VEGF阳性率,并经PCR-RFLP法测定启动子区-2578C/A、-1154G/A、-460C/T和+936C/T多态性位点基因型频率,比较各位点不同基因型血清VEGF水平、子宫内膜VEGF阳性率。经STRING数据库构建蛋白相互作用(PPI)网络图,明确VEGF基因与薄型子宫内膜易感基因之间的交互作用。结果 与对照组比较,研究组血清VEGF水平、子宫内膜VEGF阳性率显著降低(P<0.05)。两组VEGF基因启动子区-2578C/A、-1154G/A、-460C/T和+936C/T位点基因型频率分布符合Hardy-Weinberg遗传平衡(P>0.05)。两组VEGF基因启动子区-2578C/A位点、-1154G/A位点基因型、等位基因C、A、显性遗传模型、隐性遗传模型比较无差异(P>0.05)。两组VEGF基因启动子区-460C/T位点TC基因型频率比较无统计学差异(P>0.05);研究组VEGF基因启动子区-460C/T位点TT基因型频率、等位基因T频率、显性遗传模型TT基因型、隐性遗传模型TC+TT基因型频率均高于对照组(P<0.05),T基因型可增加薄型子宫内膜风险。研究组VEGF基因启动子区+936C/T位点TT基因型频率、TC基因型频率、等位基因T频率、显性遗传模型TT基因型、隐性遗传模型TC+TT基因型频率均高于对照组(P<0.05),T基因型可增加薄型子宫内膜风险。VEGF基因启动子区位点-2578C/A、-1154G/A不同基因型血清VEGF水平、子宫内膜VEGF阳性率比较差异无统计学意义(P>0.05);VEGF基因启动子区位点-460C/T、+936C/T位点携带T等位基因的基因型血清VEGF水平、子宫内膜VEGF阳性率显著降低(P<0.05)。经STRING数据库行VEGF基因的PPI网络分析表明,在薄型子宫内膜中VEGF基因与多个易感基因表达有交互作用。结论 VEGF基因启动子区-2578C/A、-1154G/A多态性位点与薄型子宫内膜无关,-460T>C、+936C<T位点多态性与薄型子宫内膜发生相关,该位点突变可增加薄型子宫内膜易感性。

Objective To investigate the relationship between the-2578C/A,-1154G/A,-460C/T,and+936C/T polymorphisms of vascular endothelial growth factor(VEGF)gene promoter region and thin endometrium.Methods Selected 100 patients with thin endometrium who visited or were hospitalized in the Fourth People's Hospital of Hengshui Gynecology Department from January to December 2023 as the study group,and 100 healthy adult women who underwent physical examinations during the same period as the control group.Detected the serum VEGF levels and endometrial VEGF positivity rates of two groups,and determind the genotype frequencies of promoter regions-2578C/A,-1154G/A,-460C/T,and+936C/T polymorphism sites using PCR-RFLP method.Compared the serum VEGF levels and endometrial VEGF positivity rates of different genotypes at each point.Constructed a protein interaction(PPI)network diagram using the STRING database to clarify the interaction between VEGF genes and susceptible genes in thin endometrium.Results Compared with the control group,the serum VEGF level and endometrial VEGF positivity rate in the study group were significantly reduced(P<0.05).The genotype frequency distribution of the-2578C/A,-1154G/A,-460C/T,and+936C/T loci in the promoter regions of two groups of VEGF genes conformed to the Hardy-Weinberg genetic balance(P>0.05).There were no significant difference in genotype,allele C,A,dominant genetic model,and recessive genetic model between two groups of VEGF gene promoter regions at-2578C/A and-1154G/A loci(P>0.05).There was no significant difference of TC genotype frequencies at the promoter region of VEGF gene-460C/T between the two groups(P>0.05).The TT genotype frequency,allele T frequency,dominant genetic model TT genotype frequency,and recessive genetic model TC+TT genotype frequency at the-460C/T locus of the VEGF gene promoter region in the research group were all higher than those in the control group(P<0.05),T genotype can increase the risk of thin endometrium.The TT genotype frequency,TC genotype frequency,allele T frequency,dominant genetic model TT genotype frequency,and recessive genetic model TC+TT genotype frequency of the VEGF gene promoter region+936C/T locus in the research group were all higher than those in the control group(P<0.05),T genotype can increase the risk of thin endometrium.There was no significant difference in serum VEGF levels and endometrial VEGF positivity rates among different genotypes of VEGF gene promoter loci-2578C/A and-1154G/A(P>0.05);the serum VEGF levels and endometrial VEGF positivity rate of genotypes carrying T alleles at the-460C/T and+936C/T promoter regions of the VEGF gene were significantly reduced(P<0.05).The PPI network analysis of VEGF genes in the STRING database showed that VEGF genes interact with the expression of multiple susceptible genes in thin endometrium.Conclusion The polymorphism loci of-2578C/A and-1154G/A in the promoter region of VEGF gene were not associated with thin endometrium,while the polymorphism loci of-460T>C and+936C T were associated with thin endometrium,and mutations in this loci could increase susceptibility to thin endometrium.