Relationship between CYP2D6*10 gene polymorphism and metoprolol therapeutic effect for hypertension
10.3969/j.issn.1008-0074.2014.02
- VernacularTitle:CYP2D6*10基因多态性与美托洛尔治疗高血压疗效的关系
- Author:
Jun YANG
;
Shuang WANG
;
Tianwei DONG
;
Libo WANG
;
Leiyi ZHANG
;
Zhiguo ZHANG
;
Lili LEI
- Publication Type:Journal Article
- Keywords:
Cytochrome P-450 CYP2D6;
Polymorphism, restriction fragment length;
Metoprolol;
Hypertension
- From:
Chinese Journal of cardiovascular Rehabilitation Medicine
2014;23(2):155-160
- CountryChina
- Language:English
-
Abstract:
Objective: To study the relationship between CYP2D6*10 gene polymorphism and metoprolol therapeutic effect for hypertension. Methods: A total of 60 patients with essential hypertension (EH) received metoprolol 47.5mg/d for 3d. After 3d the plasma metoprolol concentration after oral 2h was measured. Polymorphism of CYP2D6*10 gene was detected by PCR-RFLP. According to results of gene detection, the patients were divided into CC genotype group (wild type homozygote, fast metabolism type, n=14), CT genotype group (heterozygous mutation, intermediate metabolism type, n=25) and TT genotype group (homozygous mutation, slow metabolism, n=19). Metoprolol dosage was adjusted according to CYP2D6*10 genotype. After one week, plasma concentration of metoprolol after oral 2h was measured again, and mean heart rate and blood pressure were measured before and after gene-directed therapy. Results: Before gene-directed therapy, compared with CC and CT group there was significant increase in plasma concentration of metoprolol [(26.57±19.40) ng/ml vs. (23.88±12.86) ng/ml vs. (64.74±32.94) ng/ml, P<0.01] in TT group; compared with TT group, there were significant rise in mean systolic blood pressure [mSBP, (132.84±13.40) mmHg vs. (144.14±14.28) mmHg], mean diastolic blood pressure [mDBP, (76.95±9.07) mmHg vs. (81.36±7.33) mmHg] and mean heart rate [mHR, (69.13±11.83) times/min vs. (76.66±7.33) times/min] in CC group, P<0.05 all. After gene-directed therapy, there were no significant difference in plasma concentration of metoprolol, mSBP, mDBP and mHR among all groups, P>0.05 all; Compared with before gene-directed therapy, there was significant increase in plasma concentration of metoprolol, and significant decrease in mSBP, mDBP and mHR in CC group (P<0.05). There were no significant difference in blood pressure and heart rate between before and after treatment in CT group and TT group (P>0.05). Conclusion: CYP2D6*10 gene polymorphism affects metoprolol metabolism and its therapeutic effect on hypertension, gene-directed therapy can significantly improve drug therapeutic effect and reach ideal therapeutic goal in short time.
- Full text:P020140704398345700875.doc
