Role of VEGF Polymorphisms in the Susceptibility and Severity of Interstitial Lung Disease.

Sara Remuzgo-Martínez,David Iturbe Fernández,Leticia Lera-Gómez,Fernanda Genre,Belén Atienza-Mateo,Oreste Gualillo,Cristina Berastegui,Rosalía Laporta,José Manuel Cifrián,Verónica Pulito-Cueto,Amparo Solé,Alicia De Pablo Gafas,Víctor Manuel Mora Cuesta,Pilar Alonso Lecue,Sonia María Fernández Rozas,Raquel López-Mejías,Miguel Ángel González-Gay,María Piedad Ussetti,Virginia Pérez

doi:10.3390/biomedicines9050458

Abstract

The search for biomarkers that can help to establish an early diagnosis and prognosis of interstitial lung disease (ILD) is of potential interest. VEGF polymorphisms have been implicated in the development of several lung disorders. Consequently, we assessed, for the first time, the role of VEGF polymorphisms in the susceptibility and severity of ILD. A total of 436 Caucasian ILD patients (244 with idiopathic interstitial pneumonias (IIPs) and 192 with non-IIP) and 536 ethnically-matched healthy controls were genotyped for VEGF rs833061, rs1570360, rs2010963, rs3025020, and rs3025039 polymorphisms by TaqMan assays. Pulmonary function tests were collected from all the patients. VEGF serum levels were determined by ELISA in a subgroup of patients. No VEGF genotype, allele, carrier, or haplotype differences were found between ILD patients and controls as well as between IIP and non-IIP patients. However, an association of rs1570360 with IIP in women and also with lung function in IIP patients was found. None of the VEGF polymorphisms were associated with VEGF levels. In conclusion, our results suggest that VEGF does not seem to play a relevant role in ILD, although rs1570360 may influence the severity of ILD in women and a worse outcome in IIP patients.

Highlights

The term interstitial lung disease (ILD) comprises a large group of diseases caused by chronic inflammation and fibrosis of the alveoli wall that share similar functional, clinical, radiological, and anatomopathological characteristics
It is widely known that biomarkers involved in the pathogenesis of ILD are considered as potential targets for therapy [7,8]
We aimed to evaluate the role of five functional VEGF polymorphisms in the susceptibility and severity of ILD in a large cohort of patients

Summary

Introduction

The term interstitial lung disease (ILD) comprises a large group of diseases caused by chronic inflammation and fibrosis of the alveoli wall that share similar functional, clinical, radiological, and anatomopathological characteristics. Idiopathic pulmonary fibrosis (IPF) is the most frequent and severe IIP, characterized by a progressive dyspnea along with respiratory failure and a poor prognosis [4]. The study of potential blood biomarkers in the pathogenesis of ILD is considered to be of potential interest, since they may be used as additional tools for the early diagnosis and severity prognosis of these pathologies. They are more reproducible and easier to obtain than conventional invasive methods of diagnosis [7,8,9]

Objectives

Methods

Results

Conclusion