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Klotho Gene in Human Salt-Sensitive Hypertension.

Lorena Citterio1, Simona Delli Carpini1, Sara Lupoli2

  • 1Genomics of Renal Diseases and Hypertension Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.

Clinical Journal of the American Society of Nephrology : CJASN
|January 30, 2020
PubMed
Summary
This summary is machine-generated.

This study found that a specific Klotho gene variant (rs9536314) is linked to salt-sensitive hypertension in individuals with high blood pressure. Lower circulating alpha-Klotho levels correlate with increased blood pressure after salt loading and reduced kidney function.

Keywords:
allelesanimalsblood pressurecohort studiesdietary sodium chloridegenetics and developmentgenome-wide association studygenotypehumanshypertensionkidneymicenatriuresissaline solutionsingle nucleotide polymorphismsodium chloridetransgenic mice

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Area of Science:

  • Nephrology
  • Genetics
  • Cardiovascular Medicine

Background:

  • Hypertension is a prevalent aging-related disorder, with salt intake being a key environmental factor.
  • Reduced circulating alpha-Klotho levels, common in aging and certain diseases, may influence hypertension.
  • Transgenic mouse models show Klotho deficiency exacerbates salt-sensitive hypertension.

Purpose of the Study:

  • To investigate the association between Klotho gene polymorphisms and serum alpha-Klotho levels with salt sensitivity in humans.
  • To explore the relationship between Klotho and the pressure-natriuresis response in hypertensive patients.

Main Methods:

  • Evaluated Klotho polymorphisms and serum alpha-Klotho levels in treatment-naive hypertensive patients (n=673).
  • Assessed salt sensitivity using an acute saline infusion test, defining it as a mean blood pressure increase >4 mm Hg.
  • Analyzed 32 single nucleotide polymorphisms in the Klotho gene (KL), focusing on the pressure-natriuresis relationship.

Main Results:

  • 35% of hypertensive patients were salt sensitive.
  • The KL rs9536314 polymorphism was significantly associated with salt sensitivity (P=0.001), with GG/GT genotypes more prevalent in salt-sensitive individuals.
  • Carriers of the G allele exhibited a blunted pressure-natriuresis response.
  • Circulating alpha-Klotho showed an inverse relationship with mean blood pressure changes post-saline load (r=-0.14, P=0.03) and a positive correlation with estimated glomerular filtration rate (eGFR) (r=0.22, P<0.001).

Conclusions:

  • The KL rs9536314 polymorphism is a significant genetic factor associated with salt-sensitive hypertension in treatment-naive hypertensive patients.
  • Circulating alpha-Klotho levels are linked to diastolic blood pressure changes following salt loading and eGFR, reflecting kidney aging.