Background Both enviromental and genetic factors have been implicated in the pathogenesis of essential hypertension. The excessive sodium reabsorption due to the constitutive activation of the renal epithelial channel (ESC) leads to the development of sodiusensitive hypertension in Liddle's syndrome. The constitutive activation of ESC is caused by the truncating or missense mutations of genes for ß or gamma ESC subunits. The common polymorphism in the codon 650 of gamma ESC has been identified last year. The gamma 650 ESC polymorphism concerns the C to G transversion of the third nucleotide in the last 650 codon. Therefore, the aims of our study were to establish the method for detection of gamma 650 ESC polymorphism and subsequently to evaluate the association between gamma650 ESC polymorphism and the sodium-sensitivity of blood pressure.
Methods The study was carried out in 76 adult, lean (BMI < 25 kg/m2) Caucasian patients with essential hypertension (WHO I stage). The patients were divided into two groups: 50 subjects with sodiu-sensitive hypertension (SS) and 26 subjects with sodium-nonsensitive hypertension (SR). Genomic DNA isolated from peripheral blood nuclear cells was amplified by PCR method with primers flanking the polymorphic region. The gamma650ESC polymorphism was identified by loss of Sac I restriction site.
Results No significant differences in genotype frequency as well as allele frequency have been found between both groups (genotypes: 60.0% CC, 38.0% and 2.0% GG in SS versus 53.8% CC, 42.3% CG and 3.8% GG in SR, and alleles: 79.0% C+ 21.0% G in SS versus 75.0% C + 25.0% G in SR, respectively). The significantly higher glomerular filtration rate (GFR) and significantly lower excreted fraction of filtered sodium (FENa) have been observed in SS patients as compared with SR group. In addition, within the SS group the significantly lower GFR has been found in patients with G allele as compared with patients with wild type genotype (CC homozygotes).
Conclusions Our preliminary results suggest the high prevalence of gamma650 ESC polymorphism in Caucasians with essential hypertension and the lack of association between the gamma650ESC polymorphism and sodium-sensitivity of blood pressure.