Association of endothelial nitric oxide synthase gene G894T polymorphism and serum nitric oxide levels in patients with preeclampsia and gestational hypertension
Mehmet Nafi SakarAhmet Engin AtaySüreyya Sarıdaş DemirVuslat Lale BakırBülent DemirDeniz BalsakEmrullah AkayAyşe UlusoyFatma Ferda Verit
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Abstract:
Pregnancy-induced hypertension is one of the most important cause of maternal-fetal morbidity and mortality. Pregnancy-related hypertensive disorders are usually associated with diminished nitric oxide (NO) levels. We aimed to evaluate the role of serum NO levels and eNOS gene G894T polymorphism on hypertensive disorders of pregnancy.Eighty patients with gestational hypertension or preeclampsia, and 80 healthy pregnants were enrolled to analyze serum NO levels and G894T polymorphism of the eNOS gene. NO level was analyzed by high-performance liquid chromatography (HPLC) method. The G894T polymorphism of the eNOS gene was determined by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP).There was no significant difference between groups in terms of G894T/eNOS genotype and allele frequencies (p > 0.05). Serum NO levels were significantly lower in the patients group. In the control group, subjects with thymine-thymine (TT) genotype had significantly lower NO levels when compared to subjects with guanine-guanine (GG) or guanine-thymine (GT) genotype (p < 0.05).We failed to demonstrate an association between eNOS gene G894T polymorphism and serum NO levels in patients with pregnancy-induced hypertensive disorders. We established a relation between pregnancy-induced hypertension and low NO levels.Keywords:
Gestational hypertension
Gene polymorphism
Preeclampsia is represented by hypertension and proteinuria in pregnancy. It usually occurs after 20 gestational weeks. There are few reports on preeclampsia before 20 gestational weeks. In this case, we report a patient with chronic hypertension superimposed with preeclampsia at 13 gestational weeks.
Gestational hypertension
Chronic hypertension
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Endothelial dysfunction is a hallmark of preeclampsia and the role of nitric oxide (NO) has been extensively studied in this pregnancy complication. In recent years, hydrogen sulphide (H
Gestational hypertension
Endothelial Dysfunction
Pathophysiology
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Objectives: MicroRNAs have been observed to play a major role in various physiological processes, for instance, programmed cell death, cell division, pregnancy development, and proliferation. With the help of profiling of microRNAs in the serum of pregnant women, it is possible to link alterations in their concentration to the emergence of gestational problems. The aim of the study was to evaluate the diagnostic potential of MicroRNAs Mi 517 and Mi 526 as biomarkers in the detection of hypertension and preeclampsia. Material and methods: The study considered 53 patients who are in their first trimester of a singleton pregnancy. Participants have been divided into two study groups, one group with normal pregnancy and another group having the risk of developing preeclampsia or who developed hypertension or preeclampsia during follow-up constitute the study group. In order to collect data associated with circulating miRNAs in serum, blood samples have been collected from the participants of the study. Results: Based on the univariate regression model, increased expression of Mi 517 and 526 and parity status (primapara/multipara) has been obtained. The multivariate logistic analysis shows that independent risk factors for hypertension or preeclampsia are the presence of an R527 and being a primipara. Conclusions: The study's findings have revealed that R517s and R526s act as major indicative biomarkers in the first trimester for the detection of hypertension and preeclampsia. The circulating C19MC MicroRNA was examined as a potential early indicator of preeclampsia and hypertension in pregnant individuals.
Gestational hypertension
Univariate analysis
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To investigate the changes in serum levels of Th1- (IL-2 and TNF-alpha) and Th2-type cytokines (IL-10) and the ratios of Th1/Th2 (IL-2/IL-10 and TNF-alpha/IL-10) in preeclampsia and in gestational hypertension.Levels of IL-2, IL-10 and TNF-alpha were determined with radioimmunoassay in serum samples from 22 women with preeclampsia, 15 women with gestational hypertension and 32 normal term pregnant women. The Th1/Th2 ratios were calculated accordingly.There were no significant differences in serum levels of IL-2, IL-10 and TNF-alpha (P>0.05 for all) among normal pregnancy, gestational hypertension and preeclampsia. The ratio of serum IL-2/IL-10 was significantly higher in preeclampsia than that in controls (P < 0.05), and the ratio of TNF-alpha/IL-10 significantly higher in patients with preeclampsia than that in either controls or gestational hypertension (P<0.025 for both).Alterations of serum cytokine balance with predominance of Th1 immunity were observed in preeclampsia. These associations may offer insight into the pathogenesis of preeclampsia.
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Gestational hypertension and preeclampsia are hypertensive disorders related to pregnancy that can cause maternal morbidity and fetal growth retardation. The association of these disorders with family history remains unclear.To examine the degree of family aggregation of preeclampsia and gestational hypertension in Taiwan.The study was conducted using the data from the National Health Insurance Database of Taiwan. Delivery events in Taiwan from 1999 to 2013 were collected. Preeclampsia was identified based on the hospital diagnosis of index delivery. The family aggregation pattern of preeclampsia was assessed and analyzed using the relationship registered in the database with the patients.A total of 60,314 preeclampsia events were identified among 4,091,641 deliveries, accounting for 1.5% of the cohort. The incidence of preeclampsia increased with maternal age. A total of 768 preeclampsia events occurred in mothers who had a sororal history of preeclampsia (n = 20,704), accounting for 1.3% of all preeclampsia events (n = 60,314). Mothers who had a sororal history of preeclampsia had a relative risk (RR) of 2.6 (95% confidence interval [CI]: 2.41-2.80) for preeclampsia compared with mothers who did not have a sororal history of preeclampsia. The RR for gestational hypertension was 2.79 (95% CI: 2.36-3.3) in mothers with a positive sororal history of gestational hypertension.Having a sororal history of preeclampsia was a strong risk factor for preeclampsia and gestational hypertension in mothers in Taiwan. The pattern of family aggregation was similar at all maternal ages.
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15 to 25% of patients with gestational hypertension progress to preeclampsia.To determine the number of patients with gestational hypertension who developed preeclampsia.Observational prospective comparative and longitudinal study realized between november 2010 to december 2012. We included pregnant patients diagnosed with mild gestational hypertension who were followed during pregnancy to observe the progression to preeclampsia. We compared the clinical features of each group among those who developed and not the disease.We included a total of 146 patients, of whom 36 (25%, IC 95% 17.7-31.7%) progress to preeclampsia. In this group 3 (8%) developed mild preeclampsia and 33 (92%) severe preeclampsia, of which 8 (24%) account HELLP syndrome. The remaining 110 patients (75%), did not develop preeclampsia. From 12 (8%) patients with gestational age < to 28 weeks, 7 (58%) developed preeclampsia, 46 (31%) patients between 28-33 weeks, 12 (26%) evolved into preeclampsia, 39 (27%) patients between 34-36 weeks, 11 (28%) progressed to preeclampsia and finally 49 (34%) with pregnancy > 37 weeks, 6 (12%) developed to preeclampsia. When comparing these groups we found that a lower gestational age was more frequent the progression to preeclampsia (p < 0.004). The onset of gestational hypertension before 28 weeks was significantly associated with the progression of preeclampsia (OR 5.1 IC 95% 1.5-17.2). The weight of infants and gestational age was lower in children of women who developed the disease in comparison that those who did not (p < 0.001). There were no significance differences between both groups in relation with body mass index, maternal age, parity and antecedent of preeclampsia.The progression of gestational hypertension into preeclampsia appreciated in one of each four patients. The progression of gestational hypertension in preeclampsia was more common in preterm pregnancy. Most of the patients developed the severe form of the disease.
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( BJOG . 2021;128:1373–1382) Hypertensive disorders of pregnancy include preeclampsia, gestational hypertension (developing at or after 20 wk’ gestation), and chronic hypertension (diagnosed before 20 wk’ gestation, or before pregnancy). Of these, preeclampsia is associated with the highest risks for parturient and neonate. Gestational or chronic hypertension often develops into preeclampsia. Preeclampsia is typically defined by new proteinuria, though patients with chronic or gestational hypotension may face severe complications without the presence of proteinuria. Some countries have adopted a broader definition of preeclampsia, not requiring proteinuria for diagnosis and also using evidence of placental or maternal end-organ dysfunction. This secondary analysis of the Control of Hypertension in Pregnancy Study (CHIPS) aimed to compare the abilities of the traditional and broad definitions of preeclampsia to identify patients with chronic or gestational hypertension at risk of adverse outcomes.
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To clarify the role of endothelial cells in pregnancy-related hypertensive disorders, we studied the cytotoxic effect of sera from normal pregnant women and from gravidas with various hypertensive complications of pregnancy.We obtained serum samples from 84 Japanese women: 17 with preeclampsia, ten with gestational hypertension, six with chronic hypertension, five with chronic hypertension with superimposed preeclampsia, 21 normal gravidas, and 25 healthy nonpregnant women. Endothelial cell injury was measured by the release of radiolabeled chromium from the cells into the culture medium.The mean (+/- standard error of the mean) values of chromium 51 release in preeclampsia, gestational hypertension, chronic hypertension, chronic hypertension with superimposed preeclampsia, normal pregnancy, and healthy nonpregnant women were: 21.9 +/- 2.1, 10.0 +/- 2.0, 9.2 +/- 2.3, 12.9 +/- 0.8, 8.4 +/- 1.4, and 7.3 +/- 1.6%, respectively. Normal pregnant and nonpregnant subjects did not differ with respect to endothelial cell injury. Sera from women with preeclampsia demonstrated significantly greater endothelial cell injury than did sera from normal gravidas. Subjects with the three other categories of hypertensive disorders did not differ significantly from normal gravidas.Preeclampsia is characterized by the presence of a serum factor cytotoxic to endothelial cells. Therefore, the mechanism responsible for the increase in blood pressure differs between women with preeclampsia and those with other hypertensive disorders in pregnancy.
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Although gestational hypertension (GH) is a well-known disorder, gestational proteinuria (GP) has been far less emphasized. According to international criteria, hypertensive disorders of pregnancy include GH but not GP. Previous studies have not revealed the predictors of progression from GP to preeclampsia or those of progression from GH to preeclampsia. We aimed to determine both sets of predictors. A retrospective cohort study was conducted with singleton pregnant women who delivered at 22 gestational weeks or later. Preeclampsia was divided into three types: new onset of hypertension/proteinuria at 20 gestational weeks or later and additional new onset of other symptoms at < 7 days or at ≥ 7 days later. Of 94 women with preeclampsia, 20 exhibited proteinuria before preeclampsia, 14 experienced hypertension before preeclampsia, and 60 exhibited simultaneous new onset of both hypertension and proteinuria before preeclampsia; the outcomes of all types were similar. Of 34 women with presumptive GP, 58.8% developed preeclampsia; this proportion was significantly higher than that of 89 women with presumptive GH who developed preeclampsia (15.7%). According to multivariate logistic regression models, earlier onset of hypertension/proteinuria (before or at 34.7/33.9 gestational weeks) was a predicator for progression from presumptive GH/GP to preeclampsia (odds ratios: 1.21/1.21, P value: 0.0044/0.0477, respectively).
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