title: Influence of aquaporin-1 gene polymorphism on water retention in liver cirrhosis.
abstract: Water retention is a major clinical problem in patients with liver cirrhosis. The factors that predispose to water retention are poorly understood but may involve genetic factors. Recent research suggests that renal aquaporins may be a pathophysiological factor involved in this condition. Aquaporin-1 (AQP1) is expressed in the proximal tubule and aquaporin-2 (AQP2) in the renal collecting duct cells. The aim of our study was to investigate the distribution of single nucleotide polymorphisms (SNPs) of AQP1: rs1049305 (C/G) and AQP2: rs3741559 (A/G) and rs467323 (C/T) in 100 cirrhotic patients with ascites and to analyze their relationship with dilutional hyponatremia.
  
  
  METHODS
  Genomic DNA was extracted from peripheral blood. Genotyping for the presence of different polymorphisms was performed using the Custom Taqman SNP Genotyping Assays. The possible influence of rs1049305 (C/G) in AQP1 gene expression was evaluated by luciferase assays in vitro.
  
  
  RESULTS
  The allelic frequencies of the AQP1 gene were the following: CC = 15%; CG = 49%; GG = 36%. Patients with CC genotype had significantly lower plasma sodium concentration than those with CG or GG genotype. Luciferase assays showed that the rs1049305 (C/G) in the AQP1 gene functionally affected the expression level in vitro. In addition, we did not find any relationship between AQP2 SNPs observed and plasma sodium concentration.
  
  
  CONCLUSIONS
  Our results suggest that the rs1049305 (C/G, UTR3) AQP1 polymorphism could be involved in the genetic susceptibility to develop water retention in patients with liver cirrhosis.
authors.affiliation: Gastroenterology and Hepatology Unit, University Hospital "Marqués de Valdecilla", Faculty of Medicine, Santander, Spain. digfge@humv.es
authors.forename: Emilio
authors.initials: E
authors.lastname: Fábrega
authors.forename: Ana
authors.initials: A
authors.lastname: Berja
authors.forename: María Teresa
authors.initials: MT
authors.lastname: García-Unzueta
authors.forename: Armando
authors.initials: A
authors.lastname: Guerra-Ruiz
authors.forename: Marta
authors.initials: M
authors.lastname: Cobo
authors.forename: María
authors.initials: M
authors.lastname: López
authors.forename: Alfonso
authors.initials: A
authors.lastname: Bolado-Carrancio
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Amado
authors.forename: José Carlos
authors.initials: JC
authors.lastname: Rodríguez-Rey
authors.forename: Fernando
authors.initials: F
authors.lastname: Pons-Romero
mesh_terms: D000328:Adult; D000368:Aged; D051398:Aquaporin 1 / Q000235:genetics*; D051399:Aquaporin 2 / Q000235:genetics; D001201:Ascites / Q000235:genetics; D002478:Cells, Cultured; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007010:Hyponatremia / Q000235:genetics*; D008103:Liver Cirrhosis / Q000150:complications / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D020641:Polymorphism, Single Nucleotide; D014867:Water / Q000378:metabolism
chemical_list: D051399:Aquaporin 2; D014867:Water; D051398:Aquaporin 1