Ana M. Medeiros (Portugal)

Instituto Nacional de Saúde Doutor Ricardo Jorge Cardiovascular Research Group, R&D Unit, Department of Health Promotion and Prevention of Noncommunicable Diseases
Ana Medeiros is a PhD student in Biochemistry (University of Lisbon, Portugal). She has a MSc in Chemistry by the Instituto Superior Técnico (University of Lisbon, Portugal). Since 2005 is member of the laboratory team of Mafalda Bourbon’s Group (Cardiovascular Research Group, R&D Unit, Department of Health Promotion and Prevention of Noncommunicable Diseases at the National Institute of Health Doutor Ricardo Jorge, Lisbon, Portugal). Her area of scientific activity has been cardiovascular genetics and atherosclerosis with a special interest in Familial Hypercholesterolaemia (FH). Currently, she is a project manager of the Portuguese FH Study at the National Institute of Health (Lisbon, Portugal). She is also a collaborator member of the Biosystems & Integrative Sciences Institute (BioISI), Biomedical and Translation Research Unit (University of Lisbon, Portugal) and a member of the Familial Hypercholesterolemia Variant Curation Expert Panel (biocurator) at Clinical Genome Resource (cardiovascular working group). She has published 20 publications (mainly in top quartile of scientific journals) and 1 book chapter. The aim of her PhD project is to identify novel genetic strategies for the characterization of the FH phenotype.

Author Of 1 Presentation

 Conference Calendar

O019 - miRNA target-binding sites as regulators of genes involved in the lipid metabolism might explain the hypercholesterolaemia in FH patients (ID 903)

Session Type
Rapid Fire Session
Session Name
Rapid fire Session - Clinical (ID 39)
Session Time
16:00 - 17:30
Date
Mon, 31.05.2021
Room
Hall F
Lecture Time
16:13 - 16:18
Presenter

Abstract

Background and Aims

Familial hypercholesterolemia (FH) is due to mutations in LDLR, APOB and PCSK9, however, about 50% of clinical FH patients do not have an identifiable genetic cause. MicroRNAs (small non-coding RNAs) are negative regulators of gene expression and creation of new biding sites can be the cause of hypercholesterolaemia in mutation-negative families. The present work aims to analyse miRNAs targets as regulators of genes involved in lipid metabolism in FH patients.

Methods

A sample of 180 mutation-negative individuals (FH negative) was re-sequenced using NGS and the 3’UTR regions of LDLR, APOB and PCSK9 were analysed. miRNA-SNP database was used to predict target gain or loss of miRNA:mRNA binding sites disturbed by SNPs in the 3'UTR. Two groups of samples were additionally sequenced, 174 FH mutation-positive individuals and 143 normolipidemic individuals.

Results

Preliminary results show that 99% of the FH negative individuals present 2 SNPs predicted to gain 2 miRNA targets in the LDLR 3’UTR. Gain of these miRNA target-binding sites might negatively regulate LDLR gene expression in the liver. We have also identified 1 SNP (1 individual) predicted to lose a miRNA target in the APOB 3’UTR and 4 SNPs (14 individuals) predicted to lose miRNAs targets in the PCSK9 3’UTR. Loss of miRNA target-binding sites in APOB and PCSK9 3’UTRs can contribute to a higher expression of these genes in the liver. FH positive and normolipidemic cohorts are being analysed.

Conclusions

We have identified several SNPs that predict to gain/lose miRNAs target-binding sites that might explain the hypercholesterolaemia in FH mutation-negative.

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Presenter of 1 Presentation

 Conference Calendar

O019 - miRNA target-binding sites as regulators of genes involved in the lipid metabolism might explain the hypercholesterolaemia in FH patients (ID 903)

Session Type
Rapid Fire Session
Session Name
Rapid fire Session - Clinical (ID 39)
Session Time
16:00 - 17:30
Date
Mon, 31.05.2021
Room
Hall F
Lecture Time
16:13 - 16:18
Presenter

Abstract

Background and Aims

Familial hypercholesterolemia (FH) is due to mutations in LDLR, APOB and PCSK9, however, about 50% of clinical FH patients do not have an identifiable genetic cause. MicroRNAs (small non-coding RNAs) are negative regulators of gene expression and creation of new biding sites can be the cause of hypercholesterolaemia in mutation-negative families. The present work aims to analyse miRNAs targets as regulators of genes involved in lipid metabolism in FH patients.

Methods

A sample of 180 mutation-negative individuals (FH negative) was re-sequenced using NGS and the 3’UTR regions of LDLR, APOB and PCSK9 were analysed. miRNA-SNP database was used to predict target gain or loss of miRNA:mRNA binding sites disturbed by SNPs in the 3'UTR. Two groups of samples were additionally sequenced, 174 FH mutation-positive individuals and 143 normolipidemic individuals.

Results

Preliminary results show that 99% of the FH negative individuals present 2 SNPs predicted to gain 2 miRNA targets in the LDLR 3’UTR. Gain of these miRNA target-binding sites might negatively regulate LDLR gene expression in the liver. We have also identified 1 SNP (1 individual) predicted to lose a miRNA target in the APOB 3’UTR and 4 SNPs (14 individuals) predicted to lose miRNAs targets in the PCSK9 3’UTR. Loss of miRNA target-binding sites in APOB and PCSK9 3’UTRs can contribute to a higher expression of these genes in the liver. FH positive and normolipidemic cohorts are being analysed.

Conclusions

We have identified several SNPs that predict to gain/lose miRNAs target-binding sites that might explain the hypercholesterolaemia in FH mutation-negative.

Hide