Abstract 009: A Genetic Variant Of Regulatory Associated Protein Of Mtor Complex 1 (raptor) Is Associated With Blood Pressure

Abstract

Background: The regulatory associated protein of mTOR complex I (Raptor) is essential for the activity of the mTOR1 complex. Clinical and experimental evidence shows that the pharmacological inhibition of the mTOR complex reduces blood pressure (BP) and aldosterone (ALDO) levels. We have demonstrated in wild-type male mice that Raptor expression is regulated by ALDO and salt intake. The heterozygous raptor knockdown mice exhibited BP and ALDO changes based on age and sex. Hypothesis: Raptor genetic variants in humans are associated with sodium (Na + ) intake and BP. Methods: Study samples were obtained from the International Hypertensive Pathotype (HyperPATH) cohort. All 792 participants ( 449 male & 343 females) are of European descent with ages between (18-65) years old. Participants completed a cross-over intervention of liberal (LIB) and restricted (RES) Na + diets for 7 days each. Raptor genotyping by Multi-Ethnic Genotyping Array using Illumina platform yielded 135 single nucleotide variants (SNV) and assessed their association with systolic BP (SBP) with salt intake using JMP software. SNV rs99001846 was selected for further analysis using multivariate linear regression analyses as shown in the table. Conclusion: Carriers of the risk versus non-risk allele were associated with considerable increases in BP measurements but not with salt-sensitive BP (SSBP) and ALDO levels. To our knowledge, and despite the well-studied Raptor/mTOR pathways, no previous work has shown associations with BP in humans.