Genes TMEM136 and PPP1R12C Differentially Expressed in the Placenta Are Associated with Preeclampsia

The associations of genes differentially expressed in the placenta with the risk of preeclampsia in women in Central Russia were studied. The study was conducted on a sample of 366 pregnant women with preeclampsia and 631 women in the control group. All pregnant women underwent typing of nine specially selected SNPs of genes differentially expressed in the placenta. Associations of SNPs of candidate genes with preeclampsia were assessed using logistic regression. For polymorphisms that showed associations with PE, their functional effects were assessed in silico . It was established that the G allele rs36011588 TMEM136 was a protective factor (OR = 0.65), and the CA haplotype of the rs2532058–rs66707428 PPP1R12C was a risk factor (OR = 1.21) for the development of preeclampsia. The associations of these SNPs with developing preeclampsia may be due to their important epigenetic significance: they are located at the sites of modified histones in the regions of promoters and enhancers, in DNase-hypersensitive sites, in binding sites for regulatory proteins, and in the binding domains for transcription factors. Also, these loci are associated with the level of transcription and alternative splicing in tissues pathogenetically significant for the development of preeclampsia.