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.

The Expression of MAS1, an Angiotensin (1-7) Receptor, in the Eutopic Proliferative Endometria of Endometriosis Patients.

BACKGROUND/AIM: We demonstrated that AT1 and AT2 are expressed and both pathways balance the renin-angiotensin system in endometriosis. MAS1, a specific receptor of angiotensin (1-7), opposes AT1 pathway-associated tissue remodelling. It is not known whether MAS1 has an effect on the pathogenesis of endometriosis or not. MATERIALS AND METHODS: Ovarian endometriotic tissues (endo-Ov) and eutopic endometrial tissues (endo-Em) were obtained from 29 patients with endometrial cysts. Normal endometrial tissues (cont-Em) were obtained from patients without endometriosis. Immunohistochemical staining was performed for MAS1, AT1 and AT2 in the endometriosis-associated tissues. The mRNA levels of these receptors were examined by quantitative reverse transcription PCR. RESULTS: MAS1 was immune-positive at the apical side of the glandular epithelium in the endometriotic lesions. The MAS1 mRNA levels in endo-Ov were increased significantly, irrespective of the menstrual cycle phase. The MAS1 mRNA levels were significantly higher in the proliferative-tissues of the endometriosis patients than in those of the controls. The ratio of the MAS1 to the AT1 mRNA in the proliferative tissues was increased predominantly in the endometriosis patients compared with that in the controls. CONCLUSION: High MAS1 expression in the endometrium might promote the initiation of endometriosis via migration of proliferative tissue.

A case-control study between the STIM1 gene and hypertensive disorders of pregnancy.

Hypertensive disorders of pregnancy (HDP) is a common disease and is believed to be a multifactorial genetic disease. Stromal interaction molecule 1 (STIM1) was previously reported to regulate the concentration of Ca2+ and vascular contraction. The aim of the present study was to assess the association between HDP and single-nucleotide polymorphisms (SNPs) or haplotypes in the human STIM1 gene via case-control studies. On the basis of a database on the National Center of Biotechnology Information website, we selected five SNPs in the human STIM1 gene and performed an association study with 139 HDP patients and 162 age-matched non-HDP subjects. There were significant differences between the HDP and control groups in the genotypes (P=0.041) and recessive models (P=0.045) for rs7945554, and between the gestational hypertension and control groups in the dominant models (P=0.015) and alleles (P=0.043) for rs10458894. The haplotypes of A-T-G-G, A-C-A-G, A-T-A-G, G-T-G-C, A-T-G-C and G-C-A-C (rs7945554-rs10458894-rs7929653-rs2923956) were significantly different from those of the control group. In the logistic regression analysis, the AA genotype of rs7945554 was significantly more predominant in the HDP group than in the control group. We found HDP-sensitive SNPs and haplotypes, and the STIM1 gene was identified as a possible susceptibility gene for HDP. By providing guidance to patients with genetic factors for HDP, we may be able to help them avoid environmental factors that could increase the risk of HDP before or during pregnancy and thus prevent or delay the onset of the disease.