GNAI2 Polymorphic Variance Associates with the Salt‐Sensitivity of Blood Pressure
Authors: Frame Alissa A. , Wainford Richard D. 
Published: June 2021

Background

The salt‐sensitivity of blood pressure (BP), an exaggerated pressor response to salt intake significantly increases hypertension risk. Our prior data have demonstrated a pivotal role of brain Gαi2 proteins in determining the salt‐sensitivity of BP in multiple animal models. Critically, 2 independent GNAI2 SNPs in the Millennium Genome Project for Hypertension and Caucasian Italians have been reported to associate with hypertension risk.

Hypothesis

GNAI2 polymorphic variance will positively associate with the salt sensitivity of blood pressure in the Genetic Epidemiology of Salt Sensitivity (GenSalt) dataset.

Methods

The GenSalt Han Chinese cohort, with a mean systolic BP 130–160mmHg and no use of antihypertensive medications has been extensively defined previously. In this study the salt sensitivity of BP was defined by the observation of a greater than a 5mmHg increase in systolic BP following the transition from a 7‐day restricted (51.3 mmol/day) 7‐day to high‐sodium (307.8 mmol/day) intake (i.e., BP response to high sodium diet = BP on high‐sodium diet – BP on restricted‐sodium diet). 1000 subjects in this study underwent whole genome genotyping was conducted using the Affymetrix Genome Wide Human SNP Array AFFY_6.0. Of this population 968 have complete genotype and phenotype data and were analyzed in this study. A generalized‐estimating‐equation (GEE) logistic model with an exchangeable covariance matrix was used for binary data analysis in R Swift. A mixed effect linear regression model was used for continuous data analysis.

Results

Only SNPs rs10510755, rs9852677, and rs2282751 were present in GenSalt. SNPs rs9852677 and rs2282751 did not significantly associate with the salt‐sensitivity of BP. In contrast SNP rs10510755 was associated with the salt‐sensitivity of BP. For SNP rs10510755, the minor allele is “C” which has a MEF of 6.2% (Z‐score 1.95; P<0,05) in the GenSalt population and that “C” is observed 120 times in the sample GenSalt population of 968 subjects (or 1936 chromosomes). The GenSalt dataset contains 326 salt‐sensitive individuals in which SNP rs10510755 was identified in 118 independent subjects (≈36%). The positive association of SNP rs10510755 with the salt‐sensitivity of BP occurs independently of patient sex or age.

Conclusion

These studies suggest that there is a positive association between the GNAI2 SNP rs10510755 and the salt‐sensitivity of BP and provide a proof of concept clinical perspective for our prior studies demonstrating that brain Gαi2 proteins influence the salt‐sensitivity of BP in multiple animal models. These data suggest GNAI2 polymorphic variance represents a potential biomarker of the salt‐sensitivity of BP that may identify a specific sub‐set of salt sensitive subjects.

Support or Funding Information

This work was supported by NIH grants R01HL107330 and K02HL112718 and AHA grants 16MM32090001 and AHA17GRNT3367002 to RDW and NIH grant F31DK116501 to AAF.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.