Fábrega Emilio, Berja Ana, García-Unzueta María Teresa, Guerra-Ruiz Armando, Cobo Marta, López María, Bolado-Carrancio Alfonso, Amado José Antonio, Rodríguez-Rey José Carlos, Pons-Romero Fernando
Gastroenterology and Hepatology Unit, University Hospital "Marqués de Valdecilla", Faculty of Medicine, Santander, Spain.
Scand J Gastroenterol. 2011 Oct;46(10):1267-74. doi: 10.3109/00365521.2011.603161. Epub 2011 Jul 27.
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.
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.
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.
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.
水潴留是肝硬化患者的一个主要临床问题。导致水潴留的因素尚不清楚，但可能涉及遗传因素。最近的研究表明，肾水通道蛋白可能是参与这种情况的病理生理因素。水通道蛋白-1（AQP1）在近端小管中表达，水通道蛋白-2（AQP2）在肾集合管细胞中表达。我们研究的目的是调查100例肝硬化腹水患者中AQP1的单核苷酸多态性（SNP）：rs1049305（C/G）和AQP2的rs3741559（A/G）及rs467323（C/T）的分布情况，并分析它们与稀释性低钠血症的关系。
从外周血中提取基因组DNA。使用定制的Taqman SNP基因分型检测法对不同多态性的存在进行基因分型。通过体外荧光素酶检测评估rs1049305（C/G）对AQP1基因表达的可能影响。
AQP1基因的等位基因频率如下：CC = 15%；CG = 49%；GG = 36%。CC基因型患者的血浆钠浓度显著低于CG或GG基因型患者。荧光素酶检测表明，AQP1基因中的rs1049305（C/G）在体外功能上影响表达水平。此外，我们未发现观察到的AQP2 SNPs与血浆钠浓度之间存在任何关系。
我们的结果表明，rs1049305（C/G，UTR3）AQP1多态性可能参与肝硬化患者发生水潴留的遗传易感性。
