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Polymorphisms and haplotypes in candidate genes related to angiogenesis and endothelial dysfunction in preeclampsia.

ABSTRACT: Valenzuela and colleagues have recently reviewed some polymorphisms in important candidate genes involved in different pathogenic mechanisms related to preeclampsia (PE) and concluded that various studies in different populations have identified maternal polymorphisms associated with PE. However, we would like to contribute to some studies regarding candidate genes related to angiogenesis and endothelial dysfunction in PE performed in the Brazilian population. Specifically, genotypes and haplotypes formed by polymorphisms of VEGF, eNOS and MMP-9, along with an example of the interaction among these genes in the prediction of PE. Our suggestions may provide additional information with clinical relevance to PE susceptibility.

SUBMITTER: Luizon MR

PROVIDER: S-EPMC3337617 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Polymorphisms and haplotypes in candidate genes related to angiogenesis and endothelial dysfunction in preeclampsia.

Luizon Marcelo Rizzatti MR Palei Ana Carolina Taveiros AC Sandrim Valeria Cristina VC

Journal of pregnancy 20120405

Valenzuela and colleagues have recently reviewed some polymorphisms in important candidate genes involved in different pathogenic mechanisms related to preeclampsia (PE) and concluded that various studies in different populations have identified maternal polymorphisms associated with PE. However, we would like to contribute to some studies regarding candidate genes related to angiogenesis and endothelial dysfunction in PE performed in the Brazilian population. Specifically, genotypes and haploty ...[more]

PMID: 22570788

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Project description:IntroductionSchizophrenia is a chronic heterogenic neurodevelopment disorder. Many genes interfere in the development of SCZ. All four genes, NrCAM, PRODH, ANK3, and ANKK1, which were evaluated in this study, were previously reported to be associated with Schizophrenia. The NrCAM contributes to creating cognitive deficiencies through the CAM's signaling pathway. PRODH plays a vital role in creating SCZ negative symptoms through the signaling pathway of glutamatergic and NMDA receptors. ANK3 affects ion channel and molecular adhesion in Ranvier and initial segments of axons, leading to mental retardation, sleep disorder, and SCZ. ANKK1 encodes a protein kinase and was reported to be associated with alcohol addiction, Attention Deficit Hyperactivity Disorder (ADHD), and SCZ.MethodsThe subjects were selected from Schizophrenic patients referring to the Psychiatric Ward of Imam-Hussein Hospital and Schizophrenic Patients Support Institution (AHEBBA). 95 (30 Schizoaffective patients, 57 Paranoid patients, and 8 disorganized) patients were recruited as the subjects in the present case-control association study. 120 healthy subjects were recruited from the Tehran Medical Genetics Laboratory staff and a group of students from the Islamic Azad University of Science and Research in Tehran. The genotypes were determined with molecular genotyping techniques of PCR-RFLP, ARMS-PCR, and Cycle sequencing. Results were analyzed by the Chi-Square test using SPSS V. 24 and R, SNP STATE Package to investigate significant differences between cases and controls.ResultsThe incidence of schizophrenia was 68% and 32% among men and women, respectively. The evaluation of the allelic association between schizophrenia and all the candidate SNPs showed a significant association between NrCAM's SNP rs10235968 and SCZ (P=0.001). Haplotype T, T, C in rs10235968, rs6967368, rs3763463, respectively, within the NrCAM gene, showed significant association with schizophrenia disorder (P=0.0001).ConclusionNo association was found between other candidate SNPs and SCZ among the subjects.

Project description:IntroductionPreeclampsia is a medical condition complicated with hypertension and proteinuria during pregnancy. While preeclampsia affects approximately 5% of pregnancies, it remains without a cure. In addition, women who had preeclampsia during pregnancy have been reported to have an increased risk for cardiovascular disease later in life. However, the disease etiology and molecular mechanisms remain poorly understood. The paucity in the literature on preeclampsia associated maternal cardiovascular risk in different ethnic populations also present a need for more research. Therefore, the objective of this study was to identify cardiovascular/metabolic single nucleotide polymorphisms (SNPs), genes, and regulatory pathways associated with early-onset preeclampsia.Materials and methodsWe compared maternal DNAs from 31 women with early-onset preeclampsia with those from a control group of 29 women without preeclampsia who delivered full-term normal birthweight infants. Women with multiple gestations and/or known medical disorders associated with preeclampsia (pregestational diabetes, chronic hypertension, renal disease, hyperthyroidism, and lupus) were excluded. The MetaboChip genotyping array with approximately 197,000 SNPs associated with metabolic and cardiovascular traits was used. Single nucleotide polymorphism analysis was performed using the SNPAssoc program in R. The Truncated Product Method was used to identify significantly associated genes. Ingenuity Pathway Analysis and Ingenuity Causal Network Analysis were used to identify significantly associated disease processes and regulatory gene networks respectively.ResultsThe early-onset preeclampsia group included 45% Filipino, 26% White, 16% other Asian, and 13% Native Hawaiian and other Pacific Islanders, which did not differ from the control group. There were no SNPs associated with early-onset preeclampsia after correction for multiple comparisons. However, through gene-based tests, 68 genes and 23 cardiovascular disease-related processes were found to be significantly associated. Associated gene regulatory networks involved cellular movement, cardiovascular disease, and inflammatory disease.ConclusionsMultiple cardiovascular genes and diseases demonstrate associations with early-onset preeclampsia. This unfolds new areas of research regarding the genetic determinants of early-onset preeclampsia and their relation to future cardiovascular disease.

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Polymorphisms and haplotypes in candidate genes related to angiogenesis and endothelial dysfunction in preeclampsia.

Publications

Polymorphisms and haplotypes in candidate genes related to angiogenesis and endothelial dysfunction in preeclampsia.

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