Impact Of CYP2D6 And ADRB1 Polymorphisms On Heart Rate Of Post-PCI Patients Treated With Metoprolol

Aims: To explore the effect of CYP2D6 *10(100C>T)and ADRB1 1165 G>C polymorphisms on heart rate of Post-PCI patients treated with metoprolol succinate sustained-release tablets.Methods: 756 patients treated with metoprolol were chose from December 2013 to December 2015 in the Department of Internal Medicine,Fujian Provincial Cardiovascular Disease Institute and all the patients were received elective PCI successful,and recorded the clinical data.CYP2D6 and ADRB1 genes were genotyped by DNA microarray in all patients.According to CYP2D6 genotype,patients were divided into wild type(CYP2D6 * 1 / * 1),heterozygous mutation(CYP2D6 * 1 / * 10)and homozygous mutation group(CYP2D6 * 10 / * 10).The ADRB1 gene was also divided into wild type group(GG);heterozygous mutant(GC)and homozygous mutant group(CC)according to ADRB1 genotype.The differences of heart rate among the three groups were contrasted.All the patients were given an electrocardiogram(ECG)to record their heart rate 24 hours after taking metoprolol sustained-release tablets,of which more than 75% of patients taking drugs more than 72 hours.HR was measured at rest after patients had been sitting for 5 min before assessment.The rates of reaching target heart rate in three metabolites were compared,the target heart rate was defined as a heart rate below 70 beats per minute.Results:(1)319 inpatients were enrolled in the study.The CYP2D6 100 C > T mutant allele had an overall frequency of 57.21%,with frequencies of 19.10%(61 cases),47.30%(151 cases)and 33.50%(107 cases)for the wild-type(WW),heterozygous mutant group(WM)and homozygous mutant group(MM),respectively.The ADRB1 1165 G > C mutant allele had an overall frequency of 69.44%,with frequencies of 7.8%(25 cases),45.5%(145 cases)and 46.7%(149 cases)for the wild-type(GG),heterozygous mutation group(GC)and homozygous mutation group(CC)alleles,respectively.(2)Multi-factor analysis of variance revealed that there was a significant difference in heart rate among different CYP2D6 genotypes(P = 0.004).The mean heart rate of CYP2D6 homozygous mutant group was significantly lower than that of patients who carried wild type allele;and the dose of metoprolol(11.88mg/d,23.75mg/d and 45.7mg/d)was not statistically significant,and there was no interaction between genotype and dose.Nevertheless,this effect was not seen between different genotypes of ADRB1.(3)The rate of reaching target heart rate of WW and WM groups were lower than that in MM group: 24.6%,35.8% vs 71.0%,the differences were significant(P <0.001).Further multivariate analysis indicated that CYP2D6 genotypes into the equation after adjusting for BMI,age,diabetes,hypertension,dose and so on.Compared with MMs group,the rate of reaching target heart rate in CYP2D6 WWs group was lower than the MMs group(OR = 0.139,95% CI: 0.068-0.286,P <0.001).Patients with CYP2D6 WM genotype had significantly lower rate of reaching target heart rate than MMs(OR = 0.233,95% CI: 0.136-0.398,P <0.001).Conclusion: The heart rate of Post-PCI patients treated with metoprolol succinate sustained-release tabletswith CYP2D6 *10 homozygous mutations had a lower heart rate than those with CYP2D6 * 1 alleles,this phenomenon was not observed between the different ADRB1 genotypes.