子痫前期孕妇HIF-1a基因rs11549467G/A位点多态性和血清HIF-1a及VEGF水平表达与病情严重程度的相关性分析

目的　了解子痫前期（ preeclampsia，PE）孕妇缺氧诱导因子 1a（hypoxia inducible factor-1a，HIF-1a）基因 rs11549467 G/A位点多态性和血清 HIF-1a及血管内皮生长因子（ vascular endothelial growth factor，VEGF）水平表达与病情严重程度的相关性。方法　选取 2020年 1月～ 2021年 3月深圳市龙华区中心医院和深圳市龙华区人民医院 103例 PE孕妇作为 PE组，非 PE健康孕妇 120例作为对照组。分别检测血清 HIF-1a和 VEGF水平，同时对 HIF-1a基因 rs11549467 G/A位点多态性进行分析。结果　PE组 HIF-1a水平（ 23.92±5.06pg/ml）明显高于对照组（ 4.98±1.32pg/ ml），而 VEGF水平（ 86.37±20.64pg/ml）明显低于对照组（ 195.18±35.21pg/ml），差异有统计学意义（ t=13.0542，9.1475，均 P＜ 0.05）。重度 PE孕妇 HIF-1a水平（ 40.86±6.25pg/ml）明显高于轻度 PE孕妇（ 12.06±2.93pg/ml），而 VEGF水平（132.84±27.52pg/ml）明显低于轻度 PE孕妇（ 285.72±41.37pg/ml），不同程度 PE差异有统计学意义（t=10.631 5，7.194 3，均 P＜ 0.05）。PE组 HIF-1a基因 rs11549467 G/A位点 AA基因型和 A等位基因频率（ 36.89%和 49.03%）明显高于对照组（ 17.50%和 30.00%），差异有统计学意义（ χ2=7.374 5，4.826 7，均 P＜ 0.05）。重度 PE孕妇 HIF-1a基因 rs11549467G/A位点 AA基因型和 A等位基因频率（ 45.24%和 57.14%）明显高于轻度 PE孕妇（ 31.15%和 43.44%），差异有统计学意义（ χ2=4.208 6，4.619 7，均 P＜ 0.05）。AA基因型 PE孕妇 HIF-1a水平（ 37.96±8.13Pg/ml）明显高于 GG和 GA基因型孕妇（ 15.29±2.45pg/ml，16.38±2.93pg/ml），差异均有统计学意义（ t=6.904 2，6.157 6，均 P＜ 0.05），而 GG和 GA基因型比较差异无统计学意义（ t=0.914 5，P=0.071 8）。经 Pearson相关性分析， HIF-1a水平与病情严重程度呈正相关（r=0.617 4，P=0.035 9），而 VEGF水平与病情严重程度呈负相关（r=-0.691 3，P=0.031 1）。结论　PE孕妇 HIF-1a水平明显升高，而 VEGF水平明显降低，且与病情严重程度有关。同时 HIF-1a基因 rs11549467G/A位点多态性与病情严重程度存在一定相关性，可能与 PE发生和发展有密切关系。

Correlation of HIF-1a Gene rs11549467G/A Local Polymorphism and Levels of HIF-1a and VEGF with the Severity of Preeclampsia in Pregnant Women

Objective　To understand hypoxia inducible factor-1a (HIF-1a) in pregnant women with preeclampsia (PE) correlation between HIF-1a gene rs11549467 G/A polymorphism and serum HIF-1a and vascular endothelial growth factor (VEGF) expression with disease severity. Methods　103 pregnant women with PE from Longhua District Central Hospital and Longhua District People’s Hospital in Shenzhen from January 2020 to March 2021 were selected as PE group,and 120 cases of non-PE healthy pregnant women were selected as control group. The levels of HIF-1a and VEGF in serum were detected respectively,and polymorphism of HIF-1a gene rs11549467G/A was analyzed. Results　The level of HIF-1a in PE group(23.92±5.06pg/ml) was significantly higher than that of control group (4.98±1.32 pg/ml), while the level of VEGF(86.37±20.64 pg/ml) was significantly lower than that of control group (195.18±35.21pg/ml),the differences were statistically significant(t=13.054 2, 9.147 5, all P ＜ 0.05).The level of HIF-1a in pregnant women with severe PE(40.86±6.25pg/ml) was significantly higher than that in pregnant women with mild PE(12.06±2.93pg/ml), while the level of VEGF(132.84±27.52Pg/ml) was significantly lower than that in pregnant women with mild PE(285.72±41.37pg/ml), and there were statistically significant differences among different degrees of PE(t=10.631 5, 7.194 3, all P ＜ 0.05). The frequency of AA genotype and A allele of HIF-1a rs11549467G/A locus in PE group(36.89% and 49.03%) was significantly higher than that in control group (17.50% and 30.00%), and the differences were statistically significant(χ2=7.374 5, 4.826 7, all P ＜ 0.05).The frequency of AA genotype and A allele of HIF-1a gene rs11549467G/A locus in severe PE pregnant women (45.24% and 57.14%) was significantly higher than that in mild PE pregnant women(31.15% and 43.44%), the differences were statistically significant (χ2=4.208 6，4.619 7, all P ＜ <0.05). The level of HIF-1a in PE women with AA genotype (37.96±8.13 pg/ml) was significantly higher than that of GG and GA women(15.29±2.45 pg/ml，16.38±2.93 pg/ml), and the differences were statistically significant(t=6.904 2, 6.157 6, all P ＜ 0.05),but there was no statistically significant difference between GG and GA genotypes (t=0.914 5, P=0.071 8). According to pearson correlation analysis, the level of HIF-1a was positively correlated with disease severity(r=0.617 4, P=0.035 9), while level of VEGF was negatively correlated with disease severity(r=-0.691 3, P=0.031 1).Conclusion　The level of HIF-1a was significantly increased and level of VEGF was significantly decreased in pregnant women with PE, and it was related to with disease severity. At the same time, the polymorphism of HIF-1a rs11549467G/A was correlated with disease severity,which may be closely related to the occurrence and development of PE.