Genetic variants in the renin-angiotensin-aldosterone system and salt sensitivity of blood pressure

Objective: To examine the association between renin-angiotensin-aldosterone system (RAAS) genes and salt sensitivity of blood pressure (BP). Methods: A 7-day low-sodium dietary intervention followed by a 7-day high-sodium dietary intervention was conducted among 1906 participants living in a rural region of north China where habitual sodium intake is high. BP measurements were obtained at baseline and following each intervention using a random-zero sphygmomanometer. Results: DBP and mean arterial pressure responses increased with the number of rs4524238 A alleles in the angiotensin II receptor type 1 gene. For example, mean DBP responses (95% confidence interval) among those with genotypes G/G, G/A, and A/A were-2.53 (-2.89 to-2.18),-3.49 (-4.13 to-2.86), and-5.78 (-9.51 to-2.06) mmHg, respectively, following the low-sodium intervention (P = 0.0008). Carriers of the rare A allele of rs5479 in the hydroxysteroid (11-beta) dehydrogenase 2 gene had decreased DBP responses to low sodium (P = 0.00004). Those with the C/A and C/C genotypes had DBP responses of-0.70 (-6.62 to 5.22) and-2.71 (-4.88 to-0.54) mmHg, respectively. X chromosome renin-binding protein gene markers rs1557501 and rs2269372 were associated with SBP response to low sodium in men (P = 0.00004 and 0.0001, respectively). SBP responses (95% confidence interval) were-6.13 (-6.68 to-5.58) versus-4.07 (-4.88 to-3.26) and-6.04 (-6.57 to-5.52) versus-3.94 (-4.90 to-2.99) mmHg among men with major versus those with minor alleles of rs1557501 and rs2269372, respectively. Haplotype analyses of these genes supported our single-marker findings. Conclusion: We identified renin-angiotensin-aldosterone system variants that were predictive of salt sensitivity in a Han population with habitually high-sodium intake.