Novel Genetic Variants in the α-Adducin and Guanine Nucleotide Binding Protein β-Polypeptide 3 Genes and Salt Sensitivity of Blood Pressure

BACKGROUND: We examined the association between 12 single-nucleotide polymorphisms (SNPs) in the alpha-adducin (ADD1) and guanine nucleotide binding protein (G protein) beta-polypeptide 3 (GNB3) genes and systolic (SBP), diastolic (DBP), and mean arterial (MAP) pressure responses to salt intake. METHODS: A 7-day low-sodium (51.3 mmol sodium/day) followed by a 7-day high-sodium intervention (307.8 mmol sodium/day) was conducted among 1,906 Han participants from rural North China. Blood pressure (BP) measurements were obtained at baseline and at the end of each intervention period using a random-zero sphygmomanometer. RESULTS: We identified a significant association between a rare ADD1 variant rs17833172 and SBP, DBP, and MAP responses to high sodium (P values <0.0001) and DBP response to low sodium (P value = 0.002). Participants homozygous for the variant A allele of this marker had SBP, DBP, and MAP responses (95% confidence interval) to high salt of 1.6 (-1.8, 4.9), -0.8 (-5.6, 4.0), and -0.1 (-4.0, 3.9) mm Hg, respectively, vs. corresponding responses of 4.6 (2.5, 6.6), 1.7 (-0.2, 3.6), and 2.7 (0.9, 4.4) mm Hg, respectively, for those who were heterozygous or homozygous for the G allele. In addition, participants with at least one copy of the A allele of SNP rs1129649 of the GNB3 gene had significantly decreased MAP response to low salt compared to homozygotes for the C allele (P value = 0.004) with responses of -3.4 (-3.8, -3.0) vs. -4.2 (-4.6, -3.8) mm Hg, respectively. CONCLUSIONS: These data support a role for the ADD1 and GNB3 genes in BP salt sensitivity. Future studies aimed at replicating these novel findings are warranted.