Genetic Aspects of Preeclampsia and the HELLP Syndrome

Haram, Kjell; Mortensen, Jan Helge Seglem; Nagy, Béla

doi:10.1155/2014/910751

Cited by 89 publications

(67 citation statements)

References 93 publications

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“…The −98 A/C genotype appears to provide protection from PE development. More studies are required to verify the use of the −98A/C promoter variant for aiding PE prediction alone or in combination with genetic variants of other genes with possible diagnostic significance [53–56]. Further studies are also required in PE models to examine the impact of the polymorphism on the disease development and in order to find novel therapies.…”

Section: Resultsmentioning

confidence: 99%

Predicting the Risk to Develop Preeclampsia in the First Trimester Combining Promoter Variant -98A/C of LGALS13 (Placental Protein 13), Black Ethnicity, Previous Preeclampsia, Obesity, and Maternal Age

Madar-Shapiro¹,

Karady²,

Trahtenherts³

et al. 2017

Fetal Diagn Ther

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Background:LGALS13 (placental protein 13 [PP13]) promoter DNA polymorphisms was evaluated in predicting preeclampsia (PE), given PP13's effects on hypotension, angiogenesis, and immune tolerance. Methods: First-trimester plasma samples (49 term and 18 intermediate) of PE cases matched with 196 controls were collected from King's College Hospital, London, repository. Cell-free DNA was extracted and the LGALS13 exons were sequenced after PCR amplification. Expression of LGALS13 promoter reporter constructs was determined in BeWo trophoblast-like cells with luciferase assays. Adjusted odds ratio (OR) was calculated for the A/A genotype combined with maternal risk factors. Results: The A/A, A/C, and C/C genotypes in the -98 promoter position were in Hardy-Weinberg equilibrium in the control but not in the PE group (p < 0.036). The dominant A/A genotype had higher frequency in the PE group (p < 0.001). The A/C and C/C genotypes protected from PE (p < 0.032). The ORs to develop term and all PE, calculated for the A/A genotype, previous PE, body mass index (BMI) >35, black ethnicity, and maternal age >40 were 15.6 and 11.0, respectively (p < 0.001). In luciferase assays, the “-98A” promoter variant had lower expression than the “-98C” variant in non-differentiated (-13%, p = 0.04) and differentiated (-26%, p < 0.001) BeWo cells. Forskolin-induced differentiation led to a larger expression increase in the “-98C” variant than in the “-98A” variant (4.55-fold vs. 3.85-fold, p < 0.001). Conclusion: Lower LGALS13 (PP13) expression with the “A” nucleotide in the -98 promoter region position (compared to “C”) and high OR calculated for the A/A genotype in the -98A/C promoter region position, history of previous PE, BMI >35, advanced maternal age >40, and black ethnicity could serve to aid in PE prediction in the first trimester.

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Section: Resultsmentioning

confidence: 99%

Predicting the Risk to Develop Preeclampsia in the First Trimester Combining Promoter Variant -98A/C of LGALS13 (Placental Protein 13), Black Ethnicity, Previous Preeclampsia, Obesity, and Maternal Age

Madar-Shapiro¹,

Karady²,

Trahtenherts³

et al. 2017

Fetal Diagn Ther

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“…The syndrome of hemolysis, elevated liver enzymes and low platelets has been observed to be significantly higher in the Caucasian population, in those with delayed diagnosis of pre-eclampsia and in nulliparous patients [12]. In our population 6 out of the eight patients diagnosed with complete HELLP syndrome were para 0, one patient was para 1 and one was para 2, which showed a higher incidence in nulliparous patients.…”

Section: Discussionmentioning

confidence: 44%

“…Many genes have been implicated in the etiology of HELLP syndrome, such as the STOX1 gene, Syncytin Envelope Gene, Mannose Binding Lectin (MBL) gene polymorphism, Factor V leiden mutation, MTHFR deficiency [12]. Vascular endothelial growth factor (VEGF) and mutations of Angiotensin converting enzyme (ACE) have also been implicated in the pathogenesis [20].…”

Section: Discussionmentioning

confidence: 99%

A Study of HELLP Syndrome among Cases of Pre-Eclampsia and Eclampsia: Incidence and Correlation of Laboratory Parameters

Tiwari¹,

Bhalavi²,

Nayak³

et al. 2015

OALib

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Objective: To determine the incidence of HELLP syndrome amongst cases of Eclampsia and severe pre-eclampsia admitted to our hospital and to study the correlation of laboratory parameters with the mean arterial pressure (MAP) and with each other. Method: 238 cases of severe pre-eclampsia and eclampsia were studied for their clinical features, laboratory parameters and outcome. Cases were divided into two groups: non HELLP and complete HELLP for comparison of the maternal and perinatal outcome. The levels of Alanine Transaminase (ALT) were compared against other laboratory parameters for correlation. The mean arterial pressures (MAP) of the patients were computed to investigate whether its levels had any correlation with the derangement of ALT. Statistical analysis was done in SPSS software and spearman's correlation was run for the laboratory parameters. Results: No significant difference was seen in the maternal and perinatal mortality in the two groups. ALT showed no correlation with MAP as with LDH, platelets and hemoglobin and a weak but significant correlation with the parameters of renal function. Conclusion: Our population shows a low incidence of HELLP syndrome; the hepatic dysfunction correlates with the renal dysfunction without any correlation with the MAP.

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“…Preeclampsia is a heterogeneous group of disorders in pregnancy with de novo hypertension and proteinuria occurring after the 20th gestational week and is characterized by hypertension and proteinuria, with or without edema (Haram et al, 2014). As one of the most common pregnancy complications, preeclampsia is a mainly cause of high mortality and morbidity of both mother and child (Aali et al, 2004;Langenveld et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Common variant rs7579169 is associated with preeclampsia in Han Chinese women

Lf¹,

Zh²,

Wang³

2016

Genet. Mol. Res.

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ABSTRACT. As a heterogeneous group of disorders in pregnancy, many genetic factors are involved in the development of preeclampsia. The single nucleotide polymorphism (SNP) rs7579169, located on chromosome 2q14.2, has been shown to be associated with pregnancyinduced hypertension in Europeans. In this study, we examined whether the SNP rs7579169 is associated with the susceptibility to preeclampsia through a case-control research model in Han Chinese women. Genotypes of 145 patients with preeclampsia and 150 healthy pregnant subjects were identified by direct sequencing. The correlation between the rs7579169 genotype and the susceptibility to preeclampsia was evaluated using an unconditional logistic regression model. Although there were no differences of having the rs7579169 SNP between early onset and late onset preeclampsia, patients carrying the CT or TT genotype were more likely to develop preeclampsia than those carrying the CC genotype (CT vs CC: OR = 1.76, 95%CI = 1.07-2.87, P < 0.05; TT vs CC: OR = 5.03, 95%CI = 1.99-12.73, P < 0.05; CC vs CT + TT: OR = 2.05, 95%CI = 1.27-3.30, P < 0.05). In conclusion, although no differences of the rs7579169 SNP were identified between the early onset and late onset preeclampsia groups, we found that the CT or TT genotype and the CT+TT genotype were significantly associated with an increased risk of preeclampsia in Han Chinese women.

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Genetic Aspects of Preeclampsia and the HELLP Syndrome

Cited by 89 publications

References 93 publications

Predicting the Risk to Develop Preeclampsia in the First Trimester Combining Promoter Variant -98A/C of LGALS13 (Placental Protein 13), Black Ethnicity, Previous Preeclampsia, Obesity, and Maternal Age

Predicting the Risk to Develop Preeclampsia in the First Trimester Combining Promoter Variant -98A/C of LGALS13 (Placental Protein 13), Black Ethnicity, Previous Preeclampsia, Obesity, and Maternal Age

A Study of HELLP Syndrome among Cases of Pre-Eclampsia and Eclampsia: Incidence and Correlation of Laboratory Parameters

Common variant rs7579169 is associated with preeclampsia in Han Chinese women

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