Associations between Genetic Variants of the Natriuretic Peptide System and Blood Pressure Response to Dietary Sodium Intervention: The GenSalt Study

BACKGROUND The aim of this study was to comprehensively test the association of genetic variants in the natriuretic peptide (NP) system with blood pressure (BP) response to dietary sodium intervention in a Chinese population. METHODS We conducted a 7-day low-sodium intervention followed by a 7-day high-sodium intervention among 1,906 participants in rural China. BP measurements were obtained at baseline and each dietary intervention using a random-zero sphygmomanometer. Linear mixed-effect models were used to assess the associations of 48 single-nucleotide polymorphisms (SNPs) in 6 genes of NP system with BP response to dietary sodium intervention. RESULTS SNP rs5063 in the NPPA gene and SNP rs2077386 in the NPPC gene exhibited significant associations with BP response to low-sodium dietary intervention under recessive genetic model. For rs5063, absolute mean arterial pressure responses (95% confidence interval) to the low-sodium intervention were 1.31 (-1.08, 3.70) mm Hg for TT genotype and-3.74 (-4.01,-3.46) mm Hg for CC or TC genotype, respectively (P = 4.1 × 10^-5). Individuals with at least one copy of the C allele of rs2077386 had significantly reduction in systolic BP during the low-sodium intervention compared to those with genotype GG with responses of-5.48 (-5.83,-5.14) vs.-2.76 (-3.52,-2.00) mm Hg, respectively (P = 1.9 × 10^-13). CONCLUSIONS These novel findings suggested that genetic variants of NP system may contribute to the variation of BP response to sodium intervention in Chinese population. Certainly, replication of these results in other populations and further functional studies are warranted to clarify their role in the regulation of BP and hypertension.