CAJ | 학술논문

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±&nbsp；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。
목적：연구CYP2D6*10기인다태성여미탁락이치료고혈압료효적관계。방법：60례원발성고혈압환자구복미탁락이47.5 mg/d삼일후，측정구복미탁락이2h 적혈약농도。응용취합매련반응-한제성편단장도다태성（PCR-RFLP）방법검측CYP2D6*10기인형，근거기인검측결과고혈압병인피분위 CC형조（야생형순합자，쾌대사형，14례），CT형조（돌변잡합자，중대사형，25례）화 TT형조（돌변순합자，약대사성，19례）3조。근거CYP2D6*10기인형조정미탁락이용량，일주후，재차검측구복미탁락이2h적혈약농도，병검측기인도향치료전후적평균심솔급혈압。결과：기인도향치료전，미탁락이혈약농도 TT조현저고우 CC화 CT조[（64.74±&nbsp；32.94）ng/ml비（26.57±19.40）ng/ml비（23.88±12.86）ng/ml，P＜0.01]；여 TT조비교，CC조평균수축압[（132.84±13.40）mmHg비（144.14±14.28）mmHg]、서장압[（76.95±9.07）mmHg비（81.36±7.33） mmHg]、심솔[（69.13±11.83）차/min비（76.66±7.33）차/min]명현승고（P 균＜0.05）。기인도향치료후각조적혈약농도、평균수축압、서장압급심솔무통계학차이（P 균＞0.05）。여기인도향치료전비교，CC조치료후혈약농도현저승고，평균수축압、서장압급심솔현저강저（P＜0.05）， CT조、TT조적혈압급심솔여치료전비교무통계학차이（P＞0.05）。결론：CYP2D6*10기인다태성영향미탁락이약물대사급기치료고혈압병적료효，기인도향개체화치료가현저개선료효，단시간내체도이상치료목표。
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 effect on hypertension,gene-di-rected therapy can significantly improve drug therapeutic effect and reach ideal therapeutic goal in short time.