Haplotype-based, case-control study of myosin phosphatase target subunit 1 (PPP1R12A) gene and hypertensive disorders of pregnancy

Objective: Hypertensive disorders of pregnancy (HDP) are thought to be a multifactorial genetic disease. Myosin light chain phosphorylation, which is involved in the regulation of vascular smooth muscle contraction and relaxation and thus contributes to the maintenance of blood pressure, is related to HDP. The official symbol of the gene for the production of MYPT1 protein is PPP1R12A gene. Thus, we investigated the possibility that the PPP1R12A gene is related to HDP. Methods: Subjects were 194 pregnant women with HDP and a control group of 262 pregnant women from those women examined. Four SNVs (rs7296839, rs11114256, rs2596793, and rs2694657) were selected from the PPP1R12A gene region. The HDP group was divided according to disease type, and each group was analyzed in comparison with the control group. Results: In the association analysis using the PPP1R12A gene, there were significant differences between the control group and the superimposed preeclampsia (SPE) group for rs11114256 in allele frequency distribution (P = 0.017) and genome frequency distribution in the dominant model (P = 0.014), and for rs2694657 genotype distribution frequency in the recessive model (P = 0.018). In the association analysis using haplotypes, there was a significant difference for G-A-A-G (rs7296839-rs11114256-rs2596793-rs2694657). In an analysis of haplotype-based case-control study, there was a significant difference for G-A-A-G between the control group (0.00%) and the HDP group (2.46%) (P = 0.038). Furthermore, the G-T-A-G haplotype was significantly higher in SPE group than in control group (P = 0.011). Conclusions: The implication is that the PPP1R12A gene may be a disease-susceptibility gene for SPE.