Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
DNA Cell Biol. 2021 Feb;40(2):393-404. doi: 10.1089/dna.2020.6124. Epub 2020 Dec 22.
The objective of this study was to investigate the role of endothelial nitric oxide synthase (eNOS), matrix metalloproteinases (MMP)-9, and Bcl2-associated oncogene 6 (BAG-6) gene polymorphisms, as well as the combined role of single nucleotide polymorphisms (SNPs) in hypertensive disorders of pregnancy (HDP) patients. This case-control study consisted of women with 326 HDP and 312 healthy pregnant controls. Multiplex PCR combined with next-generation sequencing method was used for determination of gene polymorphisms. Nine SNPs were analyzed, and we classified these case samples in depth by preeclampsia (PE) non-PE or blood pressure stages. We undertook allele and genotype haplotype association studies in all the cases and in the subgroups, as well as adjust age by binary logistic regression. Furthermore, the distribution of the haplotypes formed by the nine SNPs mentioned between the HDP patients and healthy pregnant controls were analyzed. There were no statistically significant differences in the nine SNPs of eNOS, MMP-9, and BAG-6 gene allele and genotype frequencies between HDP or subtypes and controls. However, for haplotype analyses, we found that the frequencies of AGACGCCGA ( = 3.67), AGACGCGCA ( = 0.03127), and GAACACCGA ( = 0.02449) were significantly lower in the cases than in the controls. However, the haplotype of GGACGCCGA ( = 0.000686) was higher in the cases than in the controls. Our results suggested protective effect of the haplotypes AGACGCCGA, AGACGCGCA, and GAACACCGA against the development of HDP, and the haplotype GGACGCCGA was the risk factor of HDP.
本研究旨在探讨内皮型一氧化氮合酶（eNOS）、基质金属蛋白酶（MMP）-9 和 Bcl2 相关癌基因 6（BAG-6）基因多态性，以及单核苷酸多态性（SNP）在妊娠高血压疾病（HDP）患者中的作用。这项病例对照研究包括 326 名 HDP 患者和 312 名健康孕妇对照。采用多重 PCR 结合下一代测序法检测基因多态性。分析了 9 个 SNP，我们根据子痫前期（PE）、非 PE 或血压阶段对这些病例样本进行了深入分类。我们对所有病例和亚组进行了等位基因和基因型单倍型关联研究，并通过二元逻辑回归调整年龄。此外，还分析了 HDP 患者和健康孕妇对照之间这 9 个 SNP 形成的单倍型分布。HDP 或亚型与对照组之间 eNOS、MMP-9 和 BAG-6 基因的 9 个 SNP 的等位基因和基因型频率无统计学差异。然而，对于单倍型分析，我们发现 AGACGCCGA（ = 3.67）、AGACGCGCA（ = 0.03127）和 GAACACCGA（ = 0.02449）的频率在病例组中明显低于对照组。然而，GGACGCCGA（ = 0.000686）的单倍型在病例组中高于对照组。我们的结果表明，AGACGCCGA、AGACGCGCA 和 GAACACCGA 三种单倍型对 HDP 的发生有保护作用，而 GGACGCCGA 单倍型是 HDP 的危险因素。
