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. 2010 Jun;28(6):1210-20.

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

Dongfeng Gu  1 , Tanika N Kelly, James E Hixson, Jing Chen, Depei Liu, Ji-chun Chen, Dabeeru C Rao, Jianjun Mu, Jixiang Ma, Cashell E Jaquish, Treva K Rice, Charles Gu, L Lee Hamm, Paul K Whelton, Jiang He
Affiliations

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

Dongfeng Gu et al. J Hypertens. 2010 Jun.

Abstract

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.

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Conflict of interest statement

Conflict of interest statement: We declare that we have no conflict of interest.

Figures

Figure 1
Figure 1
Log p-values for the association between 181 SNPs in 11 candidate genes and systolic blood pressure, diastolic blood pressure, and mean arterial pressure responses to low (top) and high (bottom) sodium interventions. Labeled SNPs had a q-value<0.05.
Figure 1
Figure 1
Log p-values for the association between 181 SNPs in 11 candidate genes and systolic blood pressure, diastolic blood pressure, and mean arterial pressure responses to low (top) and high (bottom) sodium interventions. Labeled SNPs had a q-value<0.05.
Figure 2
Figure 2
Linkage disequilibrium structure of the AGTR1 (top) and RENBP (bottom) genes.
Figure 2
Figure 2
Linkage disequilibrium structure of the AGTR1 (top) and RENBP (bottom) genes.
See this image and copyright information in PMC

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