CYP2C19 and ABCB1 genetic polymorphisms correlate with the recurrence of ischemic cardiovascular adverse events after clopidogrel treatment

Background

This study was aimed to investigate the correlation between CYP2C19 and ABCB1 polymorphisms and the recurrence of ischemic cardiovascular adverse events in patients with coronary artery disease treated with clopidogrel.

Methods

A total of 168 patients with coronary heart disease who underwent PCI operation and received clopidogrel treatment were enrolled. Dual antiplatelet therapy was applied to the treatment of patients for 2 years. Thromboelastography was used to test the efficiency of blood coagulation. Polymerase chain reaction (PCR) was used to detect CYP2C19 and ABCB1 3435CT polymorphisms. One‐year follow‐up visit was carried out to record the incidence of cardiovascular adverse events after drug‐eluting stent implantation was inset.

Results

Follow‐up visit results suggested that the patients with high on‐treatment platelet reactivity (HPR) had a higher recurrence rate of cardiovascular adverse events after PCI operation and clopidogrel treatment. Gene polymorphism testing results indicated that patients with CYP2C19*3 had a significantly higher incidence of HPR, whereas CYP2C19*2 and ABCB1 3435CT were not significantly correlated with HPR. Multivariable logistic regression analysis showed that CYP2C19*3 might be an independent predictive factor of post‐PCI HPR. In addition, CYP2C19*3 as well as post‐PCI HPR could function as independent predictive factors of cardiovascular adverse events.

Conclusion

CYP2C19*3 polymorphism could be an important predictive factor of HPR and ischemic cardiovascular adverse events after clopidogrel treatment.

     

Progressive decline in tacrolimus clearance after renal transplantation is partially explained by decreasing CYP3A4 activity and increasing haematocrit

Aims

The long-term disposition of tacrolimus following kidney transplantation is characterized by a gradual decrease in dose requirements and increase in dose-corrected exposure. This phenomenon has been attributed to a progressive decline in cytochrome P450 3A4 (CYP3A4) activity, although this has never been demonstrated in vivo.

Methods

Sixty-five tacrolimus- and 10 cyclosporine-treated renal transplant recipients underwent pharmacokinetic testing at day 7 and months 1, 3, 6 and 12 after transplantation, including 8-h area under the concentration-time curve (AUC) for tacrolimus or cyclosporine and assessment of CYP3A4 activity using oral and intravenous midazolam (MDZ) drug probes.

Results

Tacrolimus clearance decreased gradually throughout the entire first year but only in CYP3A5*3/*3 homozygous recipients (25.6 ± 11.1 l h^–1 at day 7; 17 ± 9.1 l h^–1 at month 12; P < 0.001). In mixed model analysis, decreasing CYP3A4 activity, measured by apparent oral MDZ clearance (924 ± 443 ml min^–1 at day 7 vs. 730 ± 344 ml min^–1 at month 1; P < 0.001), explained 55.4% of the decline in tacrolimus clearance in the first month. CYP3A4 activity decreased by 18.9 ml min^–1 for every milligram of methylprednisolone dose tapering within the first month; beyond this point it remained stable. A gradual rise in haematocrit throughout the entire first year explained 31.7% of the decrease in tacrolimus clearance in the first month and 23.6% of the decrease between months 1 and 12. Cyclosporine clearance did not change over time.

Conclusions

The maturation of tacrolimus disposition in the first year after renal transplantation observed in CYP3A5*3/*3 homozygous patients can partly be explained by a (steroid tapering-related) decline in CYP3A4 activity and a progressive increase in haematocrit.     

HLA—DR2,DRB1＊0301,DQA1＊0501基因频率与肌炎及其临床表现的 …

目的：观察人类白细胞相关抗原ＨＬＡ－ＤＲ２，ＤＲＢ１＊０３０１，ＤＱＡ１＊０５０１基因频率为多发性肌炎／皮肌炎（ＰＭ／ＤＭ）发病及其临床表现的关系，方法：特异性引物聚合酶链式反应（ＰＣＲ－ＳＳＰ）方法分别测定了３１例ＰＭ／ＤＭ患者及５０例正常人的ＨＬＡ－ＤＲ２，ＤＲＢ１＊０３０１及ＨＬＡ－ＤＡＱ１＊０５０１的基因频率，结果：三种基因型在３１例肌炎患得中基频率分别为：６．４５％，９．６８％和７７．４     

自体骨髓单个核细胞移植治疗扩张型心肌病的临床研究

目的研究自体骨髓单个核细胞(ABMMNCs)经冠状动脉(冠脉)移植对扩张型心肌病(DCM)患者心功能的影响及其安全性。方法16例扩张型心肌病患者,按患者的意愿分成两组移植组(n=10)在药物治疗的同时,通过冠脉转运将ABMMNCs移植入心肌组织内;对照组(n=6)只进行相关的药物治疗;两组在术前和术后6个月分别行超声心动图及动态心电图检查。结果超声心动图检查显示移植组的左心室射血分数(LVEF)较术前明显增高,左心室舒张末期内径(LVDd)、左心室收缩末期内径(LVSd)较术前明显降低,左心房内径(LAD)也较术前明显降低。而对照组的LVEF,LVDd及LVSd虽然较6个月前有所改善,但差异无统计学意义(P>0.05)。术中及术后随访6~12个月均无恶性心律失常和其他合并症发生。结论ABMMNCs经冠脉移植,可以治疗扩张型心肌病,改善心脏功能,而且较为安全。