Genetic variants in the apelin system and blood pressure responses to dietary sodium interventions: a family-based association study.
OBJECTIVE
We examined the association between genetic variants in the apelin system and blood pressure (BP) responses to low-sodium and high-sodium interventions in the GenSalt Study.


METHODS
A 7-day low-sodium intervention (51.3 mmol sodium per day) followed by a 7-day high-sodium intervention (307.8 mmol sodium per day) was conducted among 1906 participants from 637 Han Chinese families. BP measurements were obtained at baseline and following each intervention using a random-zero sphygmomanometer. Twenty-three single nucleotide polymorphisms (SNPs), including both tag and functional SNPs, were selected from three candidate genes (APLN, APLNR, and ACE2). Single marker and haplotype analyses were conducted using the Family Based Association Test program. The false discovery rate method was used to correct for multiple testing.


RESULTS
SNPs rs2282623 and rs746886 of the APLNR gene were significantly associated with DBP (both P = 0.002) and mean arterial pressure (MAP) (P = 0.001 and 0.005, respectively) responses to low-sodium intervention. Six SNPs of the ACE2 gene were significantly associated with SBP, DBP, or MAP responses to low-sodium intervention. Three of them, rs1514283, rs1514282, and rs4646176, were also significantly associated with MAP response to high-sodium intervention (all P <or= 0.006). Haplotype analysis indicated the A-T-T haplotype of APLNR SNPs rs721608-rs2282623-rs746886 was associated with decreased DBP and MAP responses to low-sodium intervention (P = 0.001 and 0.003, respectively), whereas G-C-C was associated with increased SBP and MAP responses to high-sodium intervention (P = 0.004 and 0.01, respectively).


CONCLUSIONS
This large family-based study indicates that genetic variants in the APLNR and ACE2 genes are significantly associated with BP responses to dietary sodium intervention.
Zhao
Qi
Q
Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana 70112, USA. qizhao@tulane.edu
Hixson
James E
JE
Rao
Dabeeru C
DC
Gu
Dongfeng
D
Jaquish
Cashell E
CE
Rice
Treva
T
Shimmin
Lawrence C
LC
Chen
Jichun
J
Cao
Jie
J
Kelly
Tanika N
TN
Hamm
Lotuce Lee
LL
He
Jiang
J
D000328:Adult; D000085962:Angiotensin-Converting Enzyme 2; D000073861:Apelin; D000075244:Apelin Receptors; D001794:Blood Pressure / Q000187:drug effects* / Q000235:genetics*; D002681:China; D005006:Ethnicity; D005190:Family; D005260:Female; D006239:Haplotypes; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage / Q000494:pharmacology*
C115436:APLN protein, human; C104575:APLNR protein, human; D000073861:Apelin; D000075244:Apelin Receptors; D036341:Intercellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled; D017673:Sodium Chloride, Dietary; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2