Aquaporin-4 gene variant independently associated with oedema after intracerebral haemorrhage

Neurol Res. 2015 Aug;37(8):657-61. doi: 10.1179/1743132815Y.0000000047. Epub 2015 May 22.


Introduction: Aquaporin-4 (AQP4) is the prominent water-channel protein in the brain playing a critical role in controlling cell water content. After intracerebral haemorrhage (ICH), perihematomal oedema (PHE) formation leads to a rapid increase in intracranial pressure (ICP) after the initial bleed. We sought to investigate the effect of a common genomic variant in the AQP4 gene on PHE formation after ICH.

Methods: We reviewed the literature and identified a candidate polymorphism in AQP4 genes previously reported in Genome Wide Association Studies (GWAS). Between February 2009 and March 2011, 128 patients consented to genetic testing and were genotyped for single nucleotide polymorphism (SNP) on the AQP4 gene. Genomic DNA was extracted from buccal swabs using MasterAmp extraction kits (Epicentre, Madison, WI, USA). DNA extracted from buffy coats of whole blood samples was amplified via PCR. Linear regression with log-transformed ICH + PHE volume as the response variable was used to determine the association of SNP controlled for admission variables age, GCS, infratentorial location, hypertension, systolic blood pressure (SBP), blood urea nitrogen (BUN), glucose and alkaline phosphatase.

Results: Nine of 128 patients had the minor allele for SNP rs1058427. Presence of the minor allele was significant in the model (P = 0.021), and associated with an increase of 88% in ICH + PHE volume (β = 0.632, exp(β) = 1.88) after controlling for admission variables. The only other significant variables included in the model was GCS (P < 0.001).

Conclusion: The establishment of an independent association between rs1054827 and ICH + PHE volume provides evidence implicating the AQP4 gene in haematoma and oedema formation after ICH. Further investigation is needed to characterise this link.

Keywords: Aquaporin 4,; Candidate gene study; Genetic variant,; Intracerebral haemorrhage,; Oedema,.

MeSH terms

  • Aquaporin 4 / genetics*
  • Brain Edema / etiology*
  • Brain Edema / genetics*
  • Brain Edema / pathology
  • Brain Edema / physiopathology
  • Cerebral Hemorrhage / complications*
  • Cerebral Hemorrhage / genetics*
  • Cerebral Hemorrhage / pathology
  • Cerebral Hemorrhage / physiopathology
  • Female
  • Gene Frequency
  • Genotyping Techniques
  • Humans
  • Linear Models
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Prospective Studies


  • AQP4 protein, human
  • Aquaporin 4