Genetic variants in the ADD1 and GNB3 genes and bloodpressure response to potassium supplementation

Dietary potassium-supplementation has been associated with a decreased risk of hypertension and other cardiovascular outcomes.However,blood pressure(BP)responses to potassium supplementation vary among individuals.This study was designed to examine the association between 12 single nucleotide polymorphisms(SNPs)in the adducin 1 alpha(ADD1)and guanine nucleotide binding protein(G protein)beta polypeptide 3(GNB3)genes and systolic BP(SBP),diastolic BP(DBP),and mean arterial pressure(MAP)responses to potassium-supplementation.We conducted a 7-day high-sodium intervention(307.8 mmol sodium/day)followed by a 7-day high-sodium with potassium-supplementation(60 mmol potassium/day)among 1906 Han Chinese participants from rural north China.BP measurements were obtained at the end of each intervention period using a random-zero sphygmomanometer.We identified significant associations between ADD1 variant rs17833172 and SBP,DBP,and MAP responses to potassium-supplementation(all P<0.0001)that remained significant after adjustment for multiple comparisons.In participants that were heterozygous or homozygous for the G allele of this marker,SBP,DBP,and MAP response to potassium-supplementation were–3.52(–3.82,–3.21),–1.41(–1.66,–1.15)and–2.12(–2.37,–1.87),respectively,as compared to the corresponding responses of 1.99(0.25,3.73),–0.65(–0.10,–0.21),and–0.23(–0.37,0.83),respectively,for those who were homozygous for A allele.In addition,participants with at least one copy of the G allele of rs12503220 of the ADD1 gene had significantly increased DBP and MAP response to potassium-supplementation(P=0.0041 and 0.01,respectively),which was also significant after correction for multiple testing.DBP and MAP responses to potassiumsupplementation were–1.36(–1.63,–1.10)and–2.07(–2.32,–1.82)for those with at least G allele compared to corresponding responses of 0.86(–0.68,2.40)and–0.45(–1.74,0.84)for those who were homozygous for A allele.In summary,our study identified novel associations between genetic variants of the ADD1 gene and BP response to potassium-supplementation,which could have important clinical and public health implications.Future studies aimed at replicating these novel findings are warranted.