Seminar 4apr2019. Rare Diseases Lab 03 April 2019

The seminar will be given on Thursday 4^th of April 2019 at 10  AM, Sala de Conferencias CACTI (Torre CACTI-Planta 0).

Tittle::  “Analysis of endothelin-1 (EDN-1) UTR regions“

The speaker will be Carlos López Solarat from Rare Diseases Lab, (Vigo).

The talk will be in spanish. No registration is required.

Abstract:

Pulmonary Arterial Hypertension (PAH) is a disease characterized by an increase of secretion and deregulation of Endothelin-1 (ET-1). This peptide is secreted by the endothelium of blood vessels and promotes vasoconstriction. We carried out the characterization of the UTR regions of endothelin-1gene (EDN-1), in order to determine common variations that may modulate disease outcome.

The analysis was carried out in 60 patients with different classes of PAH, testing a fragment of 2 kb for both UTR region. An in silico analysis was performed to evaluate binding transcription factors. Luciferase assay was done to evaluate in vitro the SNP influence in gene expression. Data revealed the presence of a deletion in the promoter region (rs397751713), while a transversion in the 3’ UTR region was found (rs2859338). The distribution of the genotype frequencies in our PAH patients were: for rs397751713: A/A: 0.08; A/-: 0.27; -/-: 0.66; for rs2859338: A/A: 0.15; A/G: 0.60; G/G: 0.25. Variations are located in a KLF4 binding sequence and a vitamin D receptor binding sequence respectively. Both transcription factors are related to PAH development.

In conclusion, these SNPs in the UTR regions of EDN1 are related with gene expression levels, as we measured higher expression rates for patients with A/A and G/G genotype. Moreover, we hypothesized that this overexpression is due to the inability of KLF4 and vitamin D receptor to attach the target sequence and to regulate the expression of EDN1, as KLF4 is probe to avoid PAH when present and vitamin D is an anti-hypertrophic factor.

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