Dataset Information

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

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.

SUBMITTER: Hernandez-Pacheco N

PROVIDER: S-EPMC6037659 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Hernandez-Pacheco Natalia N Guillen-Guio Beatriz B Acosta-Herrera Marialbert M Pino-Yanes Maria M Corrales Almudena A Ambrós Alfonso A Nogales Leonor L Muriel Arturo A González-Higueras Elena E Diaz-Dominguez Francisco J FJ Zavala Elizabeth E Belda Javier J Ma Shwu-Fan SF Villar Jesús J Flores Carlos C

Intensive care medicine experimental 20180709 1

<h4>Background</h4>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.<h4>Methods</h4>We first performed a prioritization of candidate genes by integrating our own genomic data from a transcriptomic study in ...[more]

PMID: 29987654

Similar Datasets

Project description:RationaleAdiponectin is an anti-inflammatory adipokine that is the most abundant gene product of adipose tissue. Lower levels have been observed in obesity, insulin resistance, and in critical illness. However, elevated levels early in acute respiratory failure have been associated with mortality. Polymorphisms in adiponectin-related genes (ADIPOQ, ADIPOR1, ADIPOR2) have been examined for relationships with obesity, insulin resistance and diabetes, cardiovascular disease, and to circulating adipokine levels, but many gaps in knowledge remain. The current study aims to assess the association between potentially functional polymorphisms in adiponectin-related genes with acute respiratory distress syndrome (ARDS) risk and mortality.MethodsConsecutive patients with risk factors for ARDS admitted to the ICU were enrolled and followed prospectively for development of ARDS. ARDS cases were followed through day 60 for all-cause mortality. 2067 patients were successfully genotyped using the Illumina CVD BeadChip high-density platform. Of these, 567 patients developed ARDS. Forty-four single nucleotide polymorphisms (SNPs) on ADIPOQ, ADIPOR1 and ADIPOR2 were successfully genotyped. Of these, 9 SNPs were hypothesized to be functional based on their location (promoter, exon, or 3' untranslated region). These 9 SNPs were analyzed for association with ARDS case status and mortality among ARDS cases.ResultsAfter multivariable analysis and adjustment for multiple comparisons, no SNPs were significantly associated with ARDS case status. Among ARDS cases, homozygotes for the minor allele of rs2082940 (ADIPOQ) had increased mortality (hazard ratio 2.61, 95% confidence interval 1.36-5.00, p = 0.0039) after adjustment for significant covariates. The significance of this association persisted after adjustment for multiple comparisons (FDR_q = 0.029).ConclusionsA common and potentially functional polymorphism in ADIPOQ may impact survival in ARDS. Further studies are required to replicate these results and to correlate genotype with circulating adiponectin levels.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets