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Abstract: TH-OR079

Role of Klotho Genetic Polymorphisms in Salt-Sensitivity Hypertension: A Link between Salt and Aging?

Session Information

Category: Hypertension and CVD

  • 1403 Hypertension and CVD: Mechanisms

Authors

  • Lanzani, Chiara, IRCCS San Raffaele Scientific Institute, Milan, Milan, Italy
  • Fontana, Simone, IRCCS San Raffaele Scientific Institute, Milan, Milan, Italy
  • Citterio, Lorena, IRCCS San Raffaele Scientific Institute, Milan, Milan, Italy
  • Zagato, Laura, IRCCS San Raffaele Scientific Institute, Milan, Milan, Italy
  • Simonini, Marco, IRCCS San Raffaele Scientific Institute, Milan, Milan, Italy
  • Manunta, Paolo, IRCCS San Raffaele Scientific Institute, Milan, Milan, Italy
Background

Hypertension is a common aging-related disorder. Salt intake is one of the main environmental factors contributing to the development of hypertension. Recently, an elegant paper showed that one-half Klotho transgenic mice displayed a spontaneous BP increase and a salt-sensitive hypertension in response to high Na intake. Commonly, serum levels of alpha-Klotho decrease with age and this reduction may be stronger in patients with several aging-related diseases.
Aim of the study: to evaluate the role of Klotho polymorphisms in human essential hypertension and salt sensitivity.

Methods

32 SNPs in Klotho gene identified with a previous GWA were used in the genetic analysis. Selected SNPs were studied for Pressure-natriuresis relationship (PNat) in 677 naïve essential hypertensive patients, never treated before, (NHP) by Acute salt load (NaLoad: 310 mMol in 2 h iv).
Salt sensitivty (SS) is defined as mean BP increase (DMBP120) greater than 4 mm Hg at the end of infusion.

Results

We genotyped 32 SNPs within KL gene and 20 kb flanking regions. The best associated SNP with Na sensitivity resulted the missense rs9536314 common SNP, MAF 0.17 for G allele.
According to salt sensitivity definition, 64% of NHPs resulted SR, while 36 % were SS. An inverse relationship was found between plasma klotho and DMBP120. Moreover KL rs9536314 GG and GT genotypes are more represented among SS. Again, GG group shows a less steep PNat curve, that is a significant increase in MBP occurred to excrete the same quantity of salt compared to salt resistant subjects.

Conclusion

In summary, this study showed, for the first time, that KLOTHO rs9536314 polymorphism is associate to salt-sensitive hypertension by activating a right shift of the pressure-natriuresis relationship in NHP. Therefore, klotho supplement in those hypertensive patient carrying the GG o mr GT variants may be potential therapeutic strategies for the treatment of salt-sensitive hypertension and kidney damage in elderly patients.