Department of Obstetrics, The Second Children & Women's Healthcare of Jinan City, Jinan, China.
Eur Rev Med Pharmacol Sci. 2020 Oct;24(20):10338-10345. doi: 10.26355/eurrev_202010_23381.
The aim of this study was to explore the relationship between CYP11B2 gene polymorphisms and eclampsia.
A total of 400 pregnant women treated in our hospital were enrolled in this study, including 200 normal pregnant women (pregnancy group) and 200 pregnant women with eclampsia (eclampsia group). Peripheral blood was collected from subjects of the two groups. Subsequently, genomic deoxyribonucleic acids (DNAs) were extracted and amplified via polymerase chain reaction (PCR) for detection of CYP11B2 rs4543, rs3802228 and rs104894072 polymorphisms. The expression level of CYP11B2 gene was measured as well. Additionally, the correlations of CYP11B2 gene polymorphisms with blood pressure and coagulation and renal function indexes were analyzed.
The distribution of alleles of rs4543 locus in CYP11B2 gene was significantly different between eclampsia group and pregnancy group (p=0.027). The frequency of the allele C was significantly lower in eclampsia group than that of pregnancy group (p<0.05). There was a statistically significant difference in the genotype distribution of CYP11B2 rs3802228 (p=0.000) and rs104894072 (p=0.000) between eclampsia group and pregnancy group (p<0.05). Meanwhile, the frequency of AA genotype of rs3802228 and TG genotype of rs104894072 was remarkably higher in eclampsia group than that in pregnancy group (p<0.05). The distribution of the locus rs104894072 (p=0.044) in dominant model and rs3802228 (p=0.002) in recessive model in eclampsia group was different from that in pregnancy group (p<0.05). Eclampsia group showed remarkably elevated frequency of TT + TG of the locus rs104894072 in dominant model and lowered frequency of AG + GG of the locus rs3802228 in recessive model (p<0.05). Similarly, a significant difference was observed in the distribution of the haplotypes CGG (p=0.001) and TGT (p=0.048) in CYP11B2 gene between eclampsia group and pregnancy group (p<0.05). The linkage disequilibrium of the loci rs3802228 and rs104894072 was relatively high (D'=0.382). The polymorphism of the locus rs104894072 in CYP11B2 gene had an evident relation to CYP11B2 gene expression (p<0.05). Meanwhile, the expression of CYP11B2 gene was markedly higher in patients with GG genotype in eclampsia group (p<0.05). The polymorphism of CYP11B2 rs4543 was notably associated with PT level of patients in eclampsia group (p=0.000). Conversely, rs3802228 polymorphism was correlated with 24 h urine protein level (p=0.000). Besides, the proportion of patients with CGG haplotype was significantly larger among patients with systolic blood pressure of 140-160 mmHg (p<0.05). In addition, the proportion of patients with TGT haplotype was evidently greater among patients with systolic blood pressure >180 mmHg in eclampsia group (p<0.05).
CYP11B2 gene polymorphisms are significantly correlated with the development and progression of eclampsia.
本研究旨在探讨 CYP11B2 基因多态性与子痫前期的关系。
选取我院收治的 400 例孕妇作为研究对象，包括 200 例正常孕妇（妊娠组）和 200 例子痫前期孕妇（子痫前期组）。采集两组研究对象的外周血，提取基因组脱氧核糖核酸（DNA），并通过聚合酶链反应（PCR）进行 CYP11B2 rs4543、rs3802228 和 rs104894072 多态性检测，同时检测 CYP11B2 基因的表达水平。此外，分析 CYP11B2 基因多态性与血压及凝血、肾功能指标的相关性。
CYP11B2 基因 rs4543 位点的等位基因分布在子痫前期组与妊娠组间差异有统计学意义（p=0.027）。子痫前期组的等位基因 C 频率显著低于妊娠组（p<0.05）。CYP11B2 rs3802228（p=0.000）和 rs104894072（p=0.000）的基因型分布在子痫前期组与妊娠组间差异有统计学意义（p<0.05）。同时，子痫前期组 rs3802228 的 AA 基因型和 rs104894072 的 TG 基因型频率显著高于妊娠组（p<0.05）。CYP11B2 基因 rs104894072 的显性模型（p=0.044）和 rs3802228 的隐性模型（p=0.002）的位点分布在子痫前期组与妊娠组间差异有统计学意义（p<0.05）。子痫前期组 rs104894072 显性模型的 TT+TG 频率显著升高，而 rs3802228 隐性模型的 AG+GG 频率显著降低（p<0.05）。同样，CYP11B2 基因的 CGG（p=0.001）和 TGT（p=0.048）单倍型在子痫前期组与妊娠组间的分布差异有统计学意义（p<0.05）。rs3802228 和 rs104894072 之间的连锁不平衡度相对较高（D'=0.382）。CYP11B2 基因 rs104894072 多态性与 CYP11B2 基因表达有明显关系（p<0.05）。同时，子痫前期组中 GG 基因型患者的 CYP11B2 基因表达明显更高（p<0.05）。CYP11B2 rs4543 多态性与子痫前期组患者的 PT 水平显著相关（p=0.000）。相反，rs3802228 多态性与 24 h 尿蛋白水平相关（p=0.000）。此外，子痫前期组中收缩压为 140-160 mmHg 的患者中 CGG 单倍型的比例明显更大（p<0.05）。此外，子痫前期组中收缩压>180 mmHg 的患者中 TGT 单倍型的比例明显更大（p<0.05）。
CYP11B2 基因多态性与子痫前期的发生和发展密切相关。
