ROCK2 allelic variants are not associated with pre-eclampsia susceptibility in the Finnish population

Peterson, Hanna; Laivuori, Hannele; Kerkelä, Erja; Jiao, Hong; Hiltunen, Leena; Heino, Sarika; Tiala, Inkeri; Knuutila, Sakari; Rasi, Vesa; Kere, Juha; Kivinen, Katja

doi:10.1093/molehr/gap032

Cited by 7 publications

(5 citation statements)

References 28 publications

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“…The target for miR-135b predicted by the miRDB database corresponds to rho-associated coiled-coil protein kinase 2 ( ROCK2 ) known to be elevated in PE placentas ( 46 ). ROCK2 has been mapped within the PE linkage peak on chromosome 2p25 in genome-wide linkage screening ( 47 ). miR-135b is expressed in placenta tissue and found in the maternal circulation ( 48 ), confirming its feasible functional significance in pregnancy.…”

Section: Discussionmentioning

confidence: 99%

Placental microRNA expression in pregnancies complicated by superimposed pre-eclampsia on chronic hypertension

Vashukova

Glotov

Fedotov

et al. 2016

Molecular Medicine Reports

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Pre-eclampsia (PE) is a complication of pregnancy that affects 5–8% of women after 20 weeks of gestation. It is usually diagnosed based on the de novo onset of hypertension and proteinuria. Preexisting hypertension in women developing PE, also known as superimposed PE on chronic hypertension (SPE), leads to elevated risk of maternal and fetal mortality. PE is associated with an altered microRNA (miRNA) expression pattern in the placenta, suggesting that miRNA deregulation is involved in the pathogenesis of PE. Whether and how the miRNA expression pattern is changed in the SPE placenta remains unclear. The present study analyzed the placental miRNA expression profile in pregnancies complicated by SPE. miRNA expression profiles in SPE and normal placentas were investigated using an Ion Torrent sequencing system. Sequencing data were processed using a comprehensive analysis pipeline for deep miRNA sequencing (CAP-miRSeq). A total of 22 miRNAs were identified to be deregulated in placentas from patients with SPE. They included 16 miRNAs previously known to be associated with PE and 6 novel miRNAs. Among the 6 novel miRNAs, 4 were upregulated (miR-518a, miR-527, miR-518e and miR-4532) and 2 downregulated (miR-98 and miR-135b) in SPE placentas compared with controls. The present results suggest that SPE is associated with specific alterations in the placental miRNA expression pattern, which differ from alterations detected in PE placentas, and therefore, provide novel targets for further investigation of the molecular mechanisms underlying SPE pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Placental microRNA expression in pregnancies complicated by superimposed pre-eclampsia on chronic hypertension

Vashukova

Glotov

Fedotov

et al. 2016

Molecular Medicine Reports

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“…On the other hand, inhibition of ROCK2 by certain medical agents led to normotension [ 20 , 21 ]. Peterson et al [ 22 ] evaluated allelic variant of ROCK2 in women with preeclempsia and proposed that ROCK2 could be a functional target for the regulation of preeclempsia. We detected two homozygote and one heterozygote genotypes for ROCK2 in our study.…”

Section: Discussionmentioning

confidence: 99%

The Impact of Gene Polymorphisms on the Success of Anticholinergic Treatment in Children with Overactive Bladder

et al. 2015

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Aim. To determine the impact of gene polymorphisms on detrusor contraction-relaxation harmony in children with lower urinary tract symptoms (LUTS). Materials and Methods. Toilet trained children older than 5 years of age with LUTS and normal neurological examination underwent videourodynamic study. The control group was composed of age matched children with no voiding complaints. The study group who filled out the voiding dysfunction symptom score before and after the treatment received standard oxybutynin treatment and was reevaluated 1 year after treatment. Genomic DNA was isolated from all patients and subjected to PCR for amplification. Genotyping of ARGHEF10, ROCK2, ADRB3, and CYP3A4 was carried out with Polymerase Chain Reaction- Restriction Fragment Length Polymorphism (PCR-RFLP) method. Results. 34 (45%) and 42 (55%) patients were enrolled in the study and control group, respectively. ARGEF10 GG, ADRB3 TC, and CYP3A4 AG genotype patients displayed insignificant difference between pre- and posttreatment voiding dysfunction symptom score and bladder volumes. Conclusions. The polymorphism of genes in the cholinergic pathway did not significantly differ clinical parameters. On the other hand, polymorphic patients in the adrenergic pathway seemed to suffer from clinical disappointment. For this reason, we think that the neglected adrenergic pathway could be a new therapeutic target for the treatment of anticholinergic resistant LUTS in children.

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“…It has also been shown that syncytiotrophoblast cells of the placenta express ROCK2 and expression is up regulated in pre-eclampsia 77. A study examining ten polymorphisms within ROCK2 failed to detect any association with pre-eclampsia 78. This study was powered only to detect a genetic effect of 1.6, and a larger study is warranted to investigate both ROCK2 and other genes at the 2p25 locus.…”

Section: Genome-wide Screeningmentioning

confidence: 92%

The role of genetics in pre-eclampsia and potential pharmacogenomic interventions

Williams¹

2012

PGPM

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The pregnancy-specific condition pre-eclampsia not only affects the health of mother and baby during pregnancy but also has long-term consequences, increasing the chances of cardiovascular disease in later life. It is accepted that pre-eclampsia has a placental origin, but the pathogenic mechanisms leading to the systemic endothelial dysfunction characteristic of the disorder remain to be determined. In this review we discuss some key factors regarded as important in the development of pre-eclampsia, including immune maladaptation, inadequate placentation, oxidative stress, and thrombosis. Genetic factors influence all of these proposed pathophysiological mechanisms. The inherited nature of pre-eclampsia has been known for many years, and extensive genetic studies have been undertaken in this area. Genetic research offers an attractive strategy for studying the pathogenesis of pre-eclampsia as it avoids the ethical and practical difficulties of conducting basic science research during the preclinical phase of pre-eclampsia when the underlying pathological changes occur. Although pharmacogenomic studies have not yet been conducted in pre-eclampsia, a number of studies investigating treatment for essential hypertension are of relevance to therapies used in pre-eclampsia. The pharmacogenomics of antiplatelet agents, alpha and beta blockers, calcium channel blockers, and magnesium sulfate are discussed in relation to the treatment and prevention of pre-eclampsia. Pharmacogenomics offers the prospect of individualized patient treatment, ensuring swift introduction of optimal treatment whilst minimizing the use of inappropriate or ineffective drugs, thereby reducing the risk of harmful effects to both mother and baby.

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ROCK2 allelic variants are not associated with pre-eclampsia susceptibility in the Finnish population

Cited by 7 publications

References 28 publications

Placental microRNA expression in pregnancies complicated by superimposed pre-eclampsia on chronic hypertension

Placental microRNA expression in pregnancies complicated by superimposed pre-eclampsia on chronic hypertension

The Impact of Gene Polymorphisms on the Success of Anticholinergic Treatment in Children with Overactive Bladder

The role of genetics in pre-eclampsia and potential pharmacogenomic interventions

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