PhD Scientific Days 2020

Theoretical and Translational I. Posters

Revealing Genetic Variants as Possible Predictors of the Risk of Severe Aortic Manifestations in Marfan Syndrome by Genome Wide Association Study

Előadó neve

Dr. Bence, Ágg

Előadó munkahelye

Heart and Vascular Center, Semmelweis University

Előadó telefonszáma

+3630/634-23-49

Előadó e-mail címe

agg.bence@med.semmelweis-univ.hu

Az előadás címe

Revealing Genetic Variants as Possible Predictors of the Risk of Severe Aortic Manifestations in Marfan Syndrome by Genome Wide Association Study

Szerző(k) neve és munkahelye

Bence Ágg1,2, Mátyás Pétervári2, Bernadett Ruskó1, Roland Stengl1, Kálmán Benke1, Miklós Pólos1, Zsolt Bagyura1, Tamás Radovits1, Béla Merkely1, Zoltán Szabolcs1
1 Heart and Vascular Center, Semmelweis University, Budapest
2 Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest

Szekció

Theoretical and Translational I. Posters

Language of the presentation

Hungarian

Section, first choice

Theoretical and Translational Medicine

Section, second choice

Molecular Sciences

Összefoglaló szövege

Introduction: Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder caused by the mutation of the fibrillin-1 (FBN1) gene. Manifestations of the syndrome, including the possibly life threatening aortic involvement, occur in greatly diverse combinations and with varying severity. For precise cardiovascular risk stratification and thus for choosing the appropriate therapeutic strategy it is indispensable to reveal factors that are responsible for the varying expressivity.
Aim: By utilizing an unbiased approach here we aimed to reveal single nucleotide polymorphisms (SNPs) that are related to severe forms of aortic involvement.
Methods: 125 MFS and 250 age and gender matched control patients were enrolled into a genome wide association study (GWAS). MFS patients were classified based on the severity of the aortic involvement, and after the quality control of the GWAS results assessed by the Axiom Precison Medicine Research Array platform, with the use of the PLINK software we searched for SNPs significantly associated to the above defined phenotypes.
Results: Out of the 20 SNPs showing the highest association with aortic involvement 3 variants were identified that were related to the transforming growth factor ß (TGF-ß) pathway. These genes are the following: TGIF1 (p = 9.756e-06), HLF (p = 2.438e-05) and TNC (p = 6.299e-05).
Conclusions: By utilizing an unbiased target identification approach significant association with severe aortic manifestations was identified in case of three genes participating in the TGF-ß signal transduction pathway. Based on the well-known central role of TGF-ß in the development of aortic involvement, after validation, assessment of the above variants in MFS and in related disorders could facilitate the prediction of severe aortic involvement and consequently the selection of the optimal therapeutic approach.

Additional Information

Supervisor: Prof. Dr. Zoltán Szabolcs
E-mail: sziv.szabolcs@gmail.com

Bemutatás módja

Szóbeli

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

2693

Start

11:23

End

11:26

Authors (legacy)

Bence Ágg1,2, Mátyás Pétervári2, Bernadett Ruskó1, Roland Stengl1, Kálmán Benke1, Miklós Pólos1, Zsolt Bagyura1, Tamás Radovits1, Béla Merkely1, Zoltán Szabolcs1
1 Heart and Vascular Center, Semmelweis University, Budapest
2 Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest