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

  2. Ma, Shwu-Fan
  3. Guillen-Guio, Beatriz
  4. Ambrós, Alfonso
  5. Diaz-Dominguez, Francisco J.
  6. Villar, Jesús
  7. Flores, Carlos
  8. Hernandez-Pacheco, Natalia
  9. Pino-Yanes, Maria 1
  10. Muriel, Arturo
  11. Acosta-Herrera, Marialbert
  12. González-Higueras, Elena
  13. Belda, Javier
  14. Zavala, Elizabeth
  15. Corrales, Almudena
  16. Nogales, Leonor
  1. 1 Universidad de La Laguna
    info

    Universidad de La Laguna

    San Cristobal de La Laguna, España

    ROR https://ror.org/01r9z8p25

Revista:
Intensive Care Medicine Experimental

ISSN: 2197-425X

Año de publicación: 2018

Volumen: 6

Número: 1

Tipo: Artículo

DOI: 10.1186/S40635-018-0181-6 GOOGLE SCHOLAR

Otras publicaciones en: Intensive Care Medicine Experimental

Resumen

BackgroundThe 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.MethodsWe 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.ResultsThree 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).ConclusionsWe 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.

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