Genetic and Nongenetic Factors Affecting Clopidogrel Response in the Egyptian Population

被引:41
|
作者
Khalil, B. M. [1 ]
Shahin, M. H. [2 ]
Solayman, M. H. M. [2 ,6 ]
Langaee, T. [2 ]
Schaalan, M. F. [1 ,3 ]
Gong, Y. [2 ]
Hammad, L. N. [1 ]
Al-Mesallamy, H. O. [4 ]
Hamdy, N. M. [4 ]
El-Hammady, W. A. [5 ]
Johnson, J. A. [2 ,7 ]
机构
[1] Misr Int Univ, Dept Biochem, Fac Pharm, Cairo, Egypt
[2] Univ Florida, Dept Pharmacotherapy & Translat Res, Ctr Pharmacogen, Coll Pharm, Gainesville, FL USA
[3] Misr Int Univ, Dept Pharm Practice & Clin Pharm, Cairo, Egypt
[4] Ain Shams Univ, Dept Biochem, Fac Pharm, Cairo, Egypt
[5] Ain Shams Univ, Dept Cardiol, Fac Med, Cairo, Egypt
[6] Ain Shams Univ, Dept Clin Pharm, Fac Pharm, Cairo, Egypt
[7] Univ Florida, Div Cardiovasc Med, Dept Med, Gainesville, FL USA
来源
关键词
ACUTE CORONARY SYNDROMES; TIMI; 38; TRIAL; CLINICAL-OUTCOMES; CYP2C19; GENOTYPE; PLATELET REACTIVITY; P-GLYCOPROTEIN; ABCB1; RISK; PRASUGREL; PHARMACODYNAMICS;
D O I
10.1111/cts.12383
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Aspirin and clopidogrel are the mainstay oral antiplatelet regimens, yet a substantial number of major adverse cardiac events (MACE) still occur. Herein, we investigated genetic and nongenetic factors associated with clopidogrel response in Egyptians. In all, 190 Egyptians with acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI), treated with clopidogrel (75 mg/day) for at least a month, were genotyped for CYP2C19 *2, *3, *6, *8, *10, and *17, CES1 G143E and ABCB1*6 and *8. These variants along with nongenetic factors were tested for association with the risk of having MACE in clopidogrel-treated patients. CYP2C19 loss-of-function (LOF) alleles carriers had increased risk of MACE vs. noncarriers (odds ratio 2.52; 95% confidence interval 1.23-5.15, P = 0.011). In a logistic regression, CYP2C19 LOF variants (P = 0.011), age (P = 0.032), and body mass index (BMI, P = 0.039) were significantly associated with the incidence of MACE in patients taking clopidogrel. CYP2C19 genetic variants, age, and BMI are potential predictors associated with variability to clopidogrel response in Egyptians.
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页码:23 / 28
页数:6
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