Abstract: SA-PO325
Precision Medicine: Lanosterol Synthase Gene Polymorphisms Affect Body Na+ in Salt-Sensitive Hypertension
Session Information
- Hypertension and CVD: Mechanisms
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Hypertension and CVD
- 1403 Hypertension and CVD: Mechanisms
Authors
- Cuka, Ermira, San Raffaele Scientific Institute, Milan, Italy
- Lanzani, Chiara, San Raffaele Scientific Institute, Milan, Italy
- Simonini, Marco, San Raffaele Scientific Institute, Milan, Italy
- Zagato, Laura, San Raffaele Scientific Institute, Milan, Italy
- Citterio, Lorena, San Raffaele Scientific Institute, Milan, Italy
- Brioni, Elena, San Raffaele Scientific Institute, Milan, Italy
- Hamlyn, John, University of Maryland, Baltimore, Baltimore, Maryland, United States
- Delli carpini, Simona, San Raffaele Scientific Institute, Milan, Italy
- Manunta, Paolo, San Raffaele Scientific Institute, Milan, Italy
Background
For decades, it has been widely accepted that initiation of salt-induced hypertension involves a type of kidney dysfunction (natriuretic handicap) which causes salt-sensitive subjects to excrete less of a sodium load than normal subjects and to undergo abnormal increases in cardiac output, and therefore in blood pressure (BP). Our research group has reported that a Lanosterol Synthase (LSS) gene variant influences both the salt sensitivity of BP and changes in circulating Endogenous Ouabain (EO) in response to a low salt diet. Aim of the study is to explore the role of LSS genotypic variants comparing salt-sensitive (SSH) with salt-resistant (SRH) hypertensive patients for their impact on body Na+.
Methods
A large cohort (n=807) of naïve hypertensive patients (NHP) was phenotyped for salt sensitivity by giving NaCl 308 mEq/2h/iv.
Total body Na+ at the end of infusion (T120) and after recovery (T240) was assessed by calculating the differences between Na+ infused and urinary excretion.
Results
516 SRH display a decrease in systolic BP (-0.6±0.32 mmHg), while in 291 SSH, SBP increases of 11.8±0.42 mmHg.
Meanwhile, there was no difference in total body Na+ in both groups, 254.75±1.41 mEq in SRH patient and 254.02±2.03 mEq in SSH group. Moreover, LSS rs225424 AA+AC carriers retained more body Na+ both at T120 and T240 (256.81±1.52 and 255.9±1.6 mEq) than LSS CC wild-type subjects (252.66±1.72 and 251.4±1.6 mEq; p<0.01).
Conclusion
LSS gene contributes to maintaining a positive Na+ balance in SSH. In the precision medicine era, LSS gene may be considered as a "natriuretic handicap" gene.