Abstract: SA-PO342
Lanosterol Synthase (LSS) Gene as a Predictor of Kidney Dysfunction in Hypertensive Patients
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
- Simonini, Marco, San Raffaele Scientific Institute, Milan, MILANO, Italy
- Citterio, Lorena, San Raffaele Scientific Institute, Milan, MILANO, Italy
- Salvi, Erika, Istituto Besta, Milan, Italy
- Lanzani, Chiara, San Raffaele Scientific Institute, Milan, MILANO, Italy
- Messaggio, Elisabetta, San Raffaele Scientific Institute, Milan, MILANO, Italy
- Fontana, Simone, San Raffaele Scientific Institute, Milan, MILANO, Italy
- Cusi, Daniele, Bio4Dreams LifeSciences Incubator, Bresso, Italy
- Manunta, Paolo, San Raffaele Scientific Institute, Milan, MILANO, Italy
Background
Hypertension (HYP) is one of the main causes of chronic kidney disease (CKD). Recently we have proposed LSS as genotype-based risk stratification to predict accelerated eGFR decay in essential HYP patients. We tried to find a confirmation of this result in an observational study on general population.
Methods
We extracted clinical data of a general population from HYPERGENES Consortium. We also collected genetic data for LSS polymorphism that was already demonstrated as involved in kidney damage.
Results
A cohort of 3137 subjects was selected. Incidence of HYP and CKD was 49.8% and 9.1% respectively. Patients with well-known no-HYP / no-angiosclerosis related CKD (as diabetes, glomerulonephritis, ADPKD), were excluded. Population was divided into 3 classes according to age.
At different age, HYP status have a deep impact on eGFR. Indeed in young (< 50ys) eGFR is higher in HYP vs control (86.2±19.3 vs 82.7±16.3 ml/min; p=0.04); vice-versa in elder (> 65ys) HYP have a reduction in eGFR (55.7±12.9 vs 71.0±12.9 ml/min; p<0.001). No direct influence of LSS polymorphism on eGFR was observed. When LSS is considered according to HYP status and age class it is possible to observe a preservation of age-associated eGFR reduction in normotensive patients (eGFR 91.4 vs 90.1 vs 81.8 ml/min for LSS risk allele); on the other side, LSS seems to enhance eGFR reduction associated with HYP status (eGFR 84.6 vs 75.6 vs 48.0 ml/min for LSS risk allele; p=0.032; fig. 1).
Conclusion
We confirmed on a large general population the involvement of LSS gene in enhanced eGFR loose in HYP patients. Indeed patients carrying the risk allele of this specific LSS polymorphism seem to express hyper-filtration if compared to their counterparts. When exposed to a specific pathological condition as HYP, with a further increase in eGFR in early phases, this could lead to an accelerated reduction in kidney function.