Polymorphisms of ACE2 are associated with blood pressure response to cold pressor test: the GenSalt study.
BACKGROUND
Increased blood pressure (BP) reactivity to cold pressor test (CPT) is a risk factor for hypertension. Genetic factors may influence the variation of BP response to CPT among individuals. We explored the association of genetic variants in the apelin system genes (APLN, APLNR and ACE2) and BP response to CPT in a Chinese population.


METHODS
A total of 1,998 Han Chinese participants from the Genetic Epidemiology Network of Salt Sensitivity completed a CPT. The percentage changes of BP right after the end of ice-water immersion were used as the measurement of BP responses to CPT. Twenty-two single nucleotide polymorphisms (SNPs) were selected and genotyped, including both tag and potential functional SNPs of the APLN, APLNR, and ACE2 genes. A mixed-effect linear model was used to assess the association between SNPs and BP responses to CPT.


RESULTS
In women, three SNPs (rs1514283, rs4646176, and rs879922) of the ACE2 gene were significantly associated with the diastolic BP (DBP) response to CPT in the general and recessive genetic models after adjustment for multiple testing (all false discovery rate q < 0.05). There were no significant associations of polymorphisms in APLN and APLNR genes with BP responses to CPT.


CONCLUSIONS
Our study identified genetic variants in the ACE2 gene that were significantly associated with DBP responses to cold stress in the Chinese female population. Future studies are warranted to confirm these findings.
Department of Evidence Based Medicine and Division of Population Genetics, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. jianfhuang@sina.com
Jianfeng
J
Huang
Shufeng
S
Chen
Xiangfeng
X
Lu
Qi
Q
Zhao
Dabeeru C
DC
Rao
Cashell E
CE
Jaquish
James E
JE
Hixson
Jichun
J
Chen
Laiyuan
L
Wang
Jie
J
Cao
Jianxin
J
Li
Hongfan
H
Li
Jiang
J
He
De-Pei
DP
Liu
Dongfeng
D
Gu
D000293:Adolescent; D000328:Adult; D000085962:Angiotensin-Converting Enzyme 2; D000073861:Apelin; D000075244:Apelin Receptors; D044466:Asian People / Q000235:genetics; D001794:Blood Pressure / Q000235:genetics*; D003080:Cold Temperature; D005260:Female; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D043562:Receptors, G-Protein-Coupled / Q000235:genetics
C115436:APLN protein, human; C104575:APLNR protein, human; D000073861:Apelin; D000075244:Apelin Receptors; D036341:Intercellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2