Keguang Chen, Rui Zhang, Nan Guo and Rui-chen Guo*
Received: December 05, 2018; Published: December 12, 2018
*Corresponding author: Rui-chen Guo, Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Jinan, China
Warfarin and clopidogrel are commonly used anticoagulant and antiplatelet drugs, and their response and/or toxicity were significant influenced by genetic polymorphism of drug metabolizing enzymes transporters and drug targets. Different human populations can differ significantly in genetic allelic frequencies of these enzymes. This paper focuses on genotype and allele frequencies of genes which affect the pharmacokinetic and pharmacodynamic of warfarin or clopidogrel in Han Chinese population detected in our hospital, to provide guidance for the application of pharmacogenomics and clinical pharmacology.
All subjects, Han population and nonrelative, were inpatients or outpatients taking warfarin and/or clopidogrel at Qilu Hosiptal of Shandong University. Genetic polymorphisms of related enzymes were detected by fluorescence in situ hybridization (FISH).
Polymorphisms of cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) genes are closely related to individualized treatment with warfarin . Since CYP2C9*2 mutation is almost undetectable in Asian populations , we tested CYP2C9*3 (1075A>C, rs1057910) and VKORC1 (-1639G>A, rs9923231) for warfarin therapy. Results were shown in Tables 1 and 2. There was no significant difference in CYP2C9*3 gene mutation between male and female patients. Mutation frequency of A allele in VKORC1 (-1639G>A) is higher in males than in females.
CYP2C19 [3,4] and paraoxonase 1(PON1 A>G, rs662)  gene detection are mainly used for clinical medicine of clopidogrel. CYP- 2C19*2(681G>A, rs4244285) and CYP2C19*3(636G>A rs4986893) are the most common loss-of-function mutations , while CYP- 2C19*17(-806C>T, rs12248560) was associated with increased enzyme activity . Allele and genotype frequencies of CYP2C19 results were shown in Tables 3-5. Metabolic phenotype frequencies of CYP2C19 were shown in Table 6. Allele and genotype frequencies of PON1 results were shown in Table 7. These results showed that mutation frequency of A allele in CYP2C19*3(636G>A) is higher in males than in females. Metabolic phenotype of CYP2C19*2/*2 is significantly higher in females than in males. And mutation frequency of A allele in PON1(A>G) is higher in females than in males.