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.


CONCLUSIONS
We identified renin-angiotensin-aldosterone system variants that were predictive of salt sensitivity in a Han population with habitually high-sodium intake.
Gu
Dongfeng
D
Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, and Chinese National Center for Cardiovascular Disease Control and Research, Beijing, China.
Kelly
Tanika N
TN
Hixson
James E
JE
Chen
Jing
J
Liu
Depei
D
Chen
Ji-chun
JC
Rao
Dabeeru C
DC
Mu
Jianjun
J
Ma
Jixiang
J
Jaquish
Cashell E
CE
Rice
Treva K
TK
Gu
Charles
C
Hamm
L Lee
LL
Whelton
Paul K
PK
He
Jiang
J
D000293:Adolescent; D000328:Adult; D000483:Alleles; D001794:Blood Pressure / Q000187:drug effects*; D002681:China; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012084:Renin-Angiotensin System; D017673:Sodium Chloride, Dietary / Q000494:pharmacology*; D011795:Surveys and Questionnaires; D055815:Young Adult
D017673:Sodium Chloride, Dietary