Association Between eNOS, MMP-9, BAG-6 Gene Polymorphisms and Risk of Hypertensive Disorders of Pregnancy in the Northern Chinese Population

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 (p = 3.67(e-005)), AGACGCGCA (p = 0.03127), and GAACACCGA (p = 0.02449) were significantly lower in the cases than in the controls. However, the haplotype of GGACGCCGA (p = 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.