Abstract: SA-PO1100

Alfa-Adducin and Lanosterol Synthase Interaction Cause Renal Impairment in Salt Sensitive Hypertension

Session Information

  • Salt and Hypertension
    November 04, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Hypertension

  • 1104 Hypertension: Clinical and Translational - Salt and Hypertension

Authors

  • Lanzani, Chiara, San Raffaele Scientific Institute, Milan, Italy
  • Hamlyn, John, University of Maryland, Baltimore , Baltimore, Maryland, United States
  • Manunta, Paolo, HSR-Nefrologia, Milano, Italy
  • Fontana, Simone, Università Vita Salute San Raffaele, Milan, Italy
  • Maggioni, Chiara, San Raffaele Scientific Institute, Milan, Italy
  • Zagato, Laura, Ospedale San Raffaele, Milano, Italy
  • Messaggio, Elisabetta, Università San Raffaele, Milano, Italy
  • Citterio, Lorena, Università Vita-Salute - Ospedale San Raffaele, Milano, Italy
  • Simonini, Marco, San Raffaele Scientific Institute, Milan, Italy
  • Brioni, Elena, ospedale San Raffaele, Milan, Italy
  • Delli carpini, Simona, San Raffaele Hospital, Milano, Italy
Background

The study of genes involved in the development of renal damage and salt sensitive hypertension (SSH) are still unknown. Impaired renal function is considered the major determinant of salt sensitive hypertension. To explore the role of alpha-adducin (ADD1) and lanosterol synthase (LSS) genes coding for two structural proteins of cell membrane, we studied their genetic interactions that regulate renal function and arterial pressure after saline loading in naïve hypertensive patients (NHP).

Methods

Acute saline load (NaCl 308 mEq/2 h e.v.) was performed in 701 NHP (age 44.95 ± 9.61 years, male 568, female 133), where functional and hormone renal parameters were tested.

Results

Under baseline conditions NHP carriers of the genotype LSS AA (n = 57, 114.8±3.8 ml/min) have a significantly reduced GFR (p = 0.039) compared to homozygous LSS CC subjects (126.08 ± 1.6 ml /m). After acute saline test both are able to increase the filtrate. Carriers of the LSS AA genotype show a slight increase in EO from 231 ± 29 to 242 ± 35, compared to LSS CC, where instead a significant (p=0.05) reduction is observed from 252 to 220 ± 15 pMol/L. The analysis of gene*gene interactions demonstrates that NHPs carrying mutated GT ADD1 and homozygous for LSS C variants excreted the sodium load more rapidly than their wild type ADD1*LSS polymorphism counterparts (Fig 1).

Conclusion

The results of this work demonstrate: First, patients with LSS AA genotype have a reduced glomerular filtrate under basal conditions; second, LSSAA should be define EO non modulator, since the are not able to decrease EO; third, the ADD1*LSS interaction may identify those NHPs with exaggerate natriuresis after saline load.