Impact of ACE2 gene polymorphism on antihypertensive efficacy of ACE inhibitors.
Angiotensin-converting enzyme 2 (ACE2), a newly discovered member of renin-angiotensin-aldosterone system, counterbalances the actions of angiotensin-converting enzyme. The objective of our study was to assess the association between rs2106809 polymorphism in ACE2 gene and the blood pressure response to ACE inhibitors in untreated hypertensive patients. After a 2-week, double-blind placebo run-in period, either benazepril or imidapril was administered for 6 weeks to 497 patients with mild to moderate essential hypertension. The achieved changes in BP were analyzed for their association with genotypes at ACE2 gene loci. In female hypertensive patients, the genotype frequency of ACE2 rs2106809 was 36.7%, 45.2% and 18.1% for CC, CT and TT genotypes, respectively. After 6 weeks of treatment, the reductions in diastolic blood pressure were significantly greater in female patients carrying the CC or CT genotype compared with those carrying the TT genotype (9.62±6.83 or 10.2±7.2 versus 6.81±6.31 mm Hg, respectively; P=0.045, analysis of variance (ANOVA)). Moreover, the reductions in mean arterial pressure were significantly greater in female patients carrying the CC or CT genotype compared with those carrying the TT genotype (12.1±7.5 or 12.0±7.9 versus 8.38±6.83 mm Hg, respectively; P=0.035, ANOVA). In male hypertensive patients, the genotype frequency of ACE2 rs2106809 was 58.1% and 41.9% for C and T genotypes, respectively. However, no association could be observed in males. We conclude that ACE2 rs2106809 is an important predictive factor of the response to antihypertensive treatment with ACE inhibitors in Chinese female hypertensive patients.
Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China.|Shantou University Medical College, Shantou, People's Republic of China.
Y Y
YY
Chen
Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China.
D
D
Liu
Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China.
P
P
Zhang
State Key Laboratory of Medical Genomics and Shanghai Institute of Hypertension, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
J C
JC
Zhong
Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China.
C J
CJ
Zhang
Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China.
S L
SL
Wu
Division of Hypertension, Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences; Peking Union Medical College, Beijing, People's Republic of China.
Y Q
YQ
Zhang
Division of Hypertension, Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences; Peking Union Medical College, Beijing, People's Republic of China.
G Z
GZ
Liu
Department of Clinical Laboratory, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People's Republic of China.
M
M
He
Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China.
L J
LJ
Jin
Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China.
H M
HM
Yu
D000328:Adult; D000368:Aged; D000085962:Angiotensin-Converting Enzyme 2; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D062186:Arterial Pressure / Q000187:drug effects*; D044466:Asian People / Q000235:genetics; D001552:Benzazepines / Q000627:therapeutic use*; D002681:China / Q000453:epidemiology; D004311:Double-Blind Method; D005787:Gene Frequency; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D048289:Imidazolidines / Q000627:therapeutic use*; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D010597:Pharmacogenetics; D000071184:Pharmacogenomic Variants; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D057285:Precision Medicine; D011446:Prospective Studies; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000235:genetics*; D012737:Sex Factors; D013997:Time Factors; D016896:Treatment Outcome
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001552:Benzazepines; D048289:Imidazolidines; C065166:imidapril; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2; C044946:benazepril