Angiotensin-converting enzyme gene I/D genotype affected metoprolol-induced reduction in 24-hour average heart rate.
BACKGROUND
Genetic factors can influence antihypertensive response to metoprolol, and many studies focused on the relationship between the genotype in beta1-adrenergic receptor and blood pressure (BP), little was known about the association of angiotensin-converting enzyme (ACE) genotype with the therapeutic result of metoprolol. The present study aimed to investigate whether the ACE gene insertion (I)/deletion (D) polymorphism is related to the response to metoprolol in Chinese Han hypertensive patients.


METHODS
Ninety-six patients with essential hypertension received metoprolol (100 mg once daily) as monotherapy for 8 weeks. Twenty-four hours ambulatory blood pressure monitoring and dynamic electrocardiogram were performed before and after treatment. Genotyping analysis was performed using PCR. The association of the ACE gene I/D polymorphism with variations in BP and heart rate (HR) was observed after the 8-week treatment.


RESULTS
The patients with ACE gene II polymorphism showed greater reduction in 24-hour average HR than those with ID or DD polymorphisms (P = 0.045), no effect of this genotype on the reduction in seating HR or in BP was observed. After adjusting for age, gender, body mass index, BP and HR at baseline, the ACE gene I/D polymorphism was still an independent predictor for variations in 24-hour average HR.


CONCLUSIONS
The II polymorphism in ACE gene could be a candidate predictor for greater reduction in 24-hour average HR in Chinese Han hypertensive patients treated by metoprolol. Greater benefits would be obtained by patients with II polymorphism from the treatment with metoprolol. Larger studies are warranted to validate this finding.
Liu
Li-wei
LW
Key Laboratory of Clinical Trial Research in Cardiovascular Drugs, Ministry of Health, Cardiovascular Institute and Fu Wai Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100037, China.
Liu
Hong
H
Chen
Guo-Liang
GL
Huang
Yi-ling
YL
Han
Lu-lu
LL
Xu
Zhi-min
ZM
Jiang
Xiong-jing
XJ
Li
Yi-shi
YS
D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use; D005260:Female; D005838:Genotype; D006339:Heart Rate / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics; D008297:Male; D008790:Metoprolol / Q000627:therapeutic use*; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*
D000959:Antihypertensive Agents; D007703:Peptidyl-Dipeptidase A; D008790:Metoprolol