About: A vascular endothelial growth factor receptor gene variant is associated with susceptibility to acute respiratory distress syndrome

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About: A vascular endothelial growth factor receptor gene variant is associated with susceptibility to acute respiratory distress syndrome Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	A vascular endothelial growth factor receptor gene variant is associated with susceptibility to acute respiratory distress syndrome
Creator	Ambrós, Alfonso Belda, Javier González-Higueras, Elena Villar, Jesús Flores, Carlos Corrales, Almudena Guillen-Guio, Beatriz Muriel, Arturo Acosta-Herrera, Marialbert Pino-Yanes, Maria Diaz-Dominguez, Francisco Hernandez-Pacheco, Natalia Ma, Shwu-Fan Network, Gen-Sep Nogales, Leonor Zavala, Elizabeth
topic	covid:ee85be02b92d03ce46829dd19576ed29d3d8697c#this
Source	PMC
abstract	BACKGROUND: The acute respiratory distress syndrome (ARDS) is one of the main causes of mortality in adults admitted to intensive care units. Previous studies have demonstrated the existence of genetic variants involved in the susceptibility and outcomes of this syndrome. We aimed to identify novel genes implicated in sepsis-induced ARDS susceptibility. METHODS: We first performed a prioritization of candidate genes by integrating our own genomic data from a transcriptomic study in an animal model of ARDS and from the only published genome-wide association study of ARDS study in humans. Then, we selected single nucleotide polymorphisms (SNPs) from prioritized genes to conduct a case-control discovery association study in patients with sepsis-induced ARDS (n = 225) and population-based controls (n = 899). Finally, we validated our findings in an independent sample of 661 sepsis-induced ARDS cases and 234 at-risk controls. RESULTS: Three candidate genes were prioritized: dynein cytoplasmic-2 heavy chain-1, fms-related tyrosine kinase 1 (FLT1), and integrin alpha-1. Of those, a SNP from FLT1 gene (rs9513106) was associated with ARDS in the discovery study, with an odds ratio (OR) for the C allele of 0.76, 95% confidence interval (CI) 0.58–0.98 (p = 0.037). This result was replicated in an independent study (OR = 0.78, 95% CI = 0.62–0.98, p = 0.039), showing consistent direction of effects in a meta-analysis (OR = 0.77, 95% CI = 0.65–0.92, p = 0.003). CONCLUSIONS: We identified FLT1 as a novel ARDS susceptibility gene and demonstrated that integration of genomic data can be a valid procedure to identify novel susceptibility genes. These results contribute to previous firm associations and functional evidences implicating FLT1 gene in other complex traits that are mechanistically linked, through the key role of endothelium, to the pathophysiology of ARDS. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40635-018-0181-6) contains supplementary material, which is available to authorized users.
has issue date	2018-07-09(xsd:dateTime)
bibo:doi	10.1186/s40635-018-0181-6
bibo:pmid	29987654
has license	cc-by
sha1sum (hex)	ee85be02b92d03ce46829dd19576ed29d3d8697c
schema:url	https://doi.org/10.1186/s40635-018-0181-6
resource representing a document's title	A vascular endothelial growth factor receptor gene variant is associated with susceptibility to acute respiratory distress syndrome
has PubMed Central identifier	PMC6037659
has PubMed identifier	29987654
schema:publication	Intensive Care Med Exp
resource representing a document's body	covid:ee85be02b92d03ce46829dd19576ed29d3d8697c#body_text
is http://vocab.deri.ie/void#inDataset of	https://covidontheweb.inria.fr:4443/about/id/http/ns.inria.fr/covid19/ee85be02b92d03ce46829dd19576ed29d3d8697c
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