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dc.creatorCasanova, C. (Ciro)-
dc.creatorCordoba-Lanus, E. (Elizabeth)-
dc.creatorAguirre-Jaime, A. (Armando)-
dc.creatorAlmeida-González, D. (Delia)-
dc.creatorMontejo, Á. (Ángela)-
dc.creatorVaro-Cenarruzabeitia, M.N. (Miren Nerea)-
dc.creatorZulueta, J. (Javier)-
dc.creatorRodríguez-Pérez, M.C. (María C.)-
dc.creatorEspizona-Jiménez, A. (Adriana)-
dc.creatorBaz-Dávila, R. (Rebeca)-
dc.date.accessioned2020-01-07T11:11:51Z-
dc.date.available2020-01-07T11:11:51Z-
dc.date.issued2016-
dc.identifier.citationCasanova, C.; Cordoba-Lanus, E.; Aguirre-Jaime, A.; et al. "Role of HIF1A, VEGFA and VEGFR2 SNPs in the susceptibility and progression of COPD in a spanish population". Plos one. 11 (5), 2016, e0154998es
dc.identifier.issn1932-6203-
dc.identifier.urihttps://hdl.handle.net/10171/58617-
dc.description.abstractHypoxia is involved in the development of chronic inflammatory processes. Under hypoxic conditions HIF1A, VEGF and VEGFR2 are expressed and mediate the course of the resultant disease. The aim of the present study was to define the associations between tSNPs in these genes and COPD susceptibility and progression in a Spanish cohort. The T alleles in rs3025020 and rs833070 SNPs (VEGFA gene) were less frequent in the group of COPD cases and were associated with a lower risk of developing the disease (OR = 0.60; 95% CI = 0. 39-0.93; p = 0.023 and OR = 0.60; 95% CI = 0.38-0.96; p = 0.034, respectively) under a dominant model of inheritance. The haplotype in which both SNPs presented the T allele confirmed the association found (OR = 0.02; 95% CI = 0.00 to 0.66; p = 0.03). Moreover, patients with COPD carrying the T allele in homozygosis in rs3025020 SNP showed higher lung function values and this association remained constant during 3 years of follow-up. In conclusion, T allele in rs833070 and rs3025020 may confer a protective effect to COPD susceptibility in a Spanish population and the association of the SNP rs3025020 with lung function may be suggesting a role for VEGF in the progression of the disease.-
dc.description.sponsorshipThis work was supported by Fondo de Investigación en Salud-Instituto Carlos III 09/00977, http://www.isciii.es/ISCIII/es/contenidos/fd-el-instituto/ quienes-somos.shtml, author who received the funding: CC. Project was co-financed by the European Regional Development Funds. The funders had no role in study design, data collection and The chronic hypoxemia could promote the expression of proteins that are involved in the transport of oxygen (erythropoietin), in the vasculogenesis and angiogenesis (vascular endothelial growth factor, VEGF and its receptors) or by the stimulation of expression of other genes (hypoxia inducible factor -1, HIF-1). HIF-1 is a transcription factor that acts as principal regulator of oxygen homeostasis, playing a fundamental role in the physiological response to hypoxia. It is a heterodimer composed of two subunits: HIF-1α and HIF-1β. HIF-1β is a constitutive core protein, whereas expression of HIF-1α is regulated by oxygen concentration. Furthermore, there is evidence that hypoxia is involved in the development of chronic inflammatory processes [1] and factor hypoxia-1 inducible acts as a regulator of the development of inflammation [2,3]. In fact, HIF-1 can also be activated in response to several inflammatory stimuli [4,5]. Nevertheless, the possible involvement of genetic alterations in HIF1A has not been previously studied in the COPD inflammation process caused by tobacco. VEGF is one of the most important angiogenic factors. Its action depends on its interaction with specific receptors, mainly VEGFR2 (also known as KDR). These proteins are expressed in different cell types and organs, being the alveoli and pulmonary epithelium the areas with higher expression in patients with COPD [6]. Under hypoxic conditions, VEGFA and VEGFR2 gene expression are regulated by the action of HIF-1, acting in its specific binding site in the promoter. There are three genetic association studies that attempted to explore the relationship between polymorphisms in the HIF1A and VEGFA genes and the risk of COPD in a Japanese [7] and Chinese [8,9] populations, with negative results. However, Ding et al., found an haplotype in VEGFA gene that could be associated with an increased risk of COPD in Chinese population [9]. Furthermore, Sharma et al. [10] had described an association of SNPs in VEGFA gene with FEV1/FVC when studied the progress of asthma in children and Simpson et al. [11] study in population-based and asthma cohorts suggest an important role of VEGFA SNPs in airway function at different ages. The aim of the present study was to determine whether Single Nucleotide Polymorphisms (SNPs) in HIF1A, VEGFA and VEGFR2 genes are associated with susceptibility and development of COPD in a Spanish population. Materials and Methods Study population and clinical parameters Participants in the study were divided into three groups: patients with COPD, smokers without COPD and nonsmoking controls without respiratory disease (healthy controls). Patients with COPD were recruited from the pulmonary clinic at the Hospital Universitario Nuestra Señora de Candelaria from Tenerife (Spain) since 1997. Inclusion criteria were: 35 years, smoking history of 20 pack-year and FEV1/FVC ratio <0.7 measured 20 minutes after administration of 400 mg of inhaled albuterol. In addition, patients were clinically stable for at least 6 weeks prior to the evaluation of respiratory symptoms, lung function and sample collection. Individuals were excluded if they had history of other diseases like asthma or bronchiectasis, and if they had physical or mental inability to perform different tests. The control group of current smokers without COPD were selected, mostly in the pulmonary clinic at HUNSC and a small proportion was obtained from an adult general population cohort (CDC), from the Canary Islands [12] created to study the 3 most prevalent diseases in the Canary Islands: cardiovascular disease, diabetes and cancer. The inclusion criteria for this control group were 35 years, smoking history of 15 pack-year and normal lung function, defined as post bronchodilator FEV1/FVC ratio 0.7 and absence of lung diseases. As a second control group, we included healthy individuals without smoking history composed entirely by patients 35 years from the CDC study cited above. HIF1A, VEGFA and VEGFR2 SNPs in the Susceptibility and Progression of COPD PLOS ONE | DOI:10.1371/journal.pone.0154998 May 10, 2016 2 / 11 analysis, decision to publish, or preparation of the manuscript-
dc.language.isoen-
dc.rightsinfo:eu-repo/semantics/openAccess-
dc.subjectHIF1A-
dc.subjectVEGFA-
dc.subjectVEGFR2-
dc.subjectHypoxia-
dc.subjectCOPD-
dc.titleRole of HIF1A, VEGFA and VEGFR2 SNPs in the susceptibility and progression of COPD in a spanish population-
dc.typeinfo:eu-repo/semantics/article-
dc.description.noteThis is an open access article distributed under the terms of the Creative Commons Attribution License-
dc.identifier.doi10.1371/journal.pone.0154998-
dadun.citation.endingPage11-
dadun.citation.number5-
dadun.citation.publicationNamePlos one-
dadun.citation.startingPage1-
dadun.citation.volume11-

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