CYP2D6*10基因多态性与美托洛尔治疗高血压疗效的关系(英文)  

Relationship between CYP2D6*10 gene polymorphism and metoprolol therapeutic effect for hypertension

作　　者：杨军[1] 王爽[1] 董天崴[1] 王立波[1] 张磊艺[1] 张志国[1] 雷力力[1] 

机构地区：[1]佳木斯大学附属第一医院心内一科,黑龙江佳木斯154002

出　　处：《心血管康复医学杂志》2014年第2期155-159,共5页Chinese Journal of Cardiovascular Rehabilitation Medicine

基　　金：Natural science foundation project of Heilongjiang Province(D201186);scientific research item of health department of Heilongjiang Province(2012-179)~~

摘　　要：目的:研究CYP2D6*10基因多态性与美托洛尔治疗高血压疗效的关系。方法:60例原发性高血压患者口服美托洛尔47.5 mg/d三日后,测定口服美托洛尔2h的血药浓度。应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测CYP2D6*10基因型,根据基因检测结果高血压病人被分为CC型组(野生型纯合子,快代谢型,14例),CT型组(突变杂合子,中代谢型,25例)和TT型组(突变纯合子,弱代谢性,19例)3组。根据CYP2D6*10基因型调整美托洛尔用量,一周后,再次检测口服美托洛尔2h的血药浓度,并检测基因导向治疗前后的平均心率及血压。结果:基因导向治疗前,美托洛尔血药浓度TT组显著高于CC和CT组[(64.74±32.94)ng/ml比(26.57±19.40)ng/ml比(23.88±12.86)ng/ml,P<0.01];与TT组比较,CC组平均收缩压[(132.84±13.40)mmHg比(144.14±14.28)mmHg]、舒张压[(76.95±9.07)mmHg比(81.36±7.33)mmHg]、心率[(69.13±11.83)次/min比(76.66±7.33)次/min]明显升高(P均<0.05)。基因导向治疗后各组的血药浓度、平均收缩压、舒张压及心率无统计学差异(P均>0.05)。与基因导向治疗前比较,CC组治疗后血药浓度显著升高,平均收缩压、舒张压及心率显著降低(P<0.05),CT组、TT组的血压及心率与治疗前比较无统计学差异(P>0.05)。结论:CYP2D6*10基因多态性影响美托洛尔药物代谢及其治疗高血压病的疗效,基因导向个体化治疗可显著改善疗效,短时间内达到理想治疗目标。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 in-to CC genotype group （Wild type homozygote,fast metabolism type,n=14）,CT genotype group （heterozygous mu-tation,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 af-ter gene-directed therapy.Results：Before gene-directed therapy,compared With CC and CT group there Was signif-icant 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 [mD-BP,（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 differ-ence 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 signifi-cant 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 eff

关 键 词：细胞色素P450 CYP2D6 多态性 限制性片段长度 美托洛尔 高血压 

分 类 号：R544.109[医药卫生—心血管疾病]