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Abstract
Aim: To explore the effect of CYP2D6*10 (100C > T) and ADRB1 1165 G > C polymorphisms on heart rate of post-PCI (percutaneous coronary intervention) patients treated with metoprolol succinate sustained-release tablets. Methods: A total of 756 inpatients with metoprolol succinate sustained-release tablets were selected and the genotypes of CYP2D6*10 and ADRB1 1165G > C were detected in 319 patients using gene chip detection. The target heart rate was defined as a resting heart rate < 70 beats/min. Clinical data were collected. Results: A total of 319 inpatients were enrolled in the study. The mutant allele frequencies of CYP2D6 and ADRB1 were 57.21 and 69.44%, respectively. Whatever the dose of metoprolol, the heart rates were lower in patients with homozygous mutation of CYP2D6 than those with heterozygous mutation and wild-type (p < 0.05). Nevertheless, this effect was not seen between different genotypes of ADRB1. Logistic regression analysis showed that the dose of metoprolol and the genotypes of CYP2D6 were predictors of heart rate <70 beats/min in these patients. Further multivariate analysis indicated that patients with homozygous mutation had better control of heart rates compared with those with wild-type and heterozygous mutation of CYP2D6*10 genotypes (all: p < 0.001). Conclusion:CYP2D6*10 polymorphisms were associated with the heart rate of post-PCI patients treated with metoprolol succinate sustained-release tablets.
The morbidity of coronary disease rises continually in China. The number of percutaneous coronary intervention (PCI) is increasing, but the in-hospital mortality did not decrease because of inadequate application of beta-blockers and ACE I or ARB.
Metoprolol is a lipophilic β-1 selective adrenergic receptor antagonist which is widely used for post-PCI, hypertension, heart failure and arrhythmia. The treatment effect of metoprolol is different in patients and mechanism of it had been researched in White people, but reserved controversial.
There are significant differences between CYP2D6 and ADRB1 polymorphisms among different races.
Patients & methods
A total of 319 inpatients were genotyped. The heart rate was registered from the electrocardiogram record, and target heart rate was defined as a resting heart rate <70 beats/minute.
Heart rate, dose of metoprolol and other clinical data were compared among groups.
The genotypes of CYP2D6*10 and ADRB1 1165G > C were detected by gene chip detection.
Results
Mutant allele frequencies of 57.21 and 69.44% were obtained for CYP2D6 and ADRB1, respectively.
Multiple analysis of variance indicated that patients with homozygous mutatation of CYP2D6 genotype (MM) had a lower heart rate than those with heterozygous mutation (WM) and wild-types (WW) at every dose of metoprolol (p < 0.05). There was no significant interaction for CYP2D6 polymorphism and the dose of metoprolol. Nevertheless, this effect was not seen in different genotypes of ADRB1.
The predictors of heart rate <70 beats/min were dose of metoprolol and the genotypes of CYP2D6. In addition, the treatment of metoprolol was significantly better in CYP2D6 MMs compared with WWs. In individuals with the *1*10 genotype, the rate of reaching target heart rate was lower than that in MMs.
Conclusion
CYP2D6 polymorphisms influence the heart rate of post-PCI patients treated with metoprolol.
Acknowledgements
The authors sincerely thank all the investigators and coordinators who contributed to this study.
Financial & competing interests disclosure
The supporting funding: National Natural Science Foundation of China (no. 81373838). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
Ethical conduct of research
The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.