PCR-Fluorescence Probe

*1,*2,*3 and *17 gene variants

1. High Specificity: The use of Taqman-MGB probe method, effectively enhance the genotyping specificity. 2. High Accuracy: Paraffin sealed sample, the whole process is carried out in a closed tube with beta -actin internal control system that effectively prevents product contamination and false negatives. 3. High Sensitivity: accurate genotyping of CYP2C19 down to 1ng/μL in DNA samples. 4. Simplicity and Fastness: the kit is simple and easy to operate, the detection cycle is short (1.5 hours), and the result is reliable.

Tests/Kit Packaging 12 8 PCR reaction tubes 

Sample Type:         EDTA anticoagulant venous whole blood sample.

Applicable Instrument Model:         - AB 7500 and AB 7900 fluorescent quantitative PCR instrument.           - SLAN-48P and SLAN-96P fluorescence quantitative PCR instrument.

Clopidogrel (Plavix) is an oral antiplatelet drug that can be used to prevent and treat myocardial infarction, ischemic cerebral thrombosis, occlusive vasculitis, atherosclerosis and thromboembolism caused complications. However, Clopidogrel must be biologically converted in the body into an active product to inhibit platelets’ aggregation. This biotransformation process requires cytochrome P450 encoded by the CYP2C19 gene in the liver metabolism, and the active product can selectively and irreversibly block the diphosphate adenosine-dependent platelet aggregation. The CYP2C19 gene loci alleles 681, 636 and -806 Clopidogrel metabolic enzymes are closely related to its anticoagulant effect, and Clopidogrel dose varies significantly among different patients’ genotype.   The study confirmed that CYP2C19 gene wild type CYP2C19*1/*1 type, CYP2C19*2 type, CYP2C19*3 type and CYP2C19*17 are the Chinese population more common alleles, of which CYP2C19*2 and CYP2C19*3 types can cause CYP2C19 gene encoding enzyme activity loss, carriers are called weak metabolizers. The CYP2C19*17 type can cause CYP2C19 gene encoding enzyme activity increase, and carriers are called fast metabolizers. In January 2009, Harvard University, Jessica L.M. et al., published the results of clinical research in the New England Journal of Medicine, confirming that the risk of embolism and the incidence of cardio-cerebrovascular events were increased, and the mortality rate was higher when the CYP2C19 gene mutation resulted in weak metabolism individuals. It was necessary to increase the dosage of Clopidogrel to achieve the effect of blocking platelet aggregation. Therefore, the CYP2C19 gene mutation detection has an important clinical significance in Clopidogrel personalized medication realization and cardiovascular diseases mortality rate reduction.   In March 12, 2010 the U.S. Food and Drug Administration (FDA) added a "black box warning to the label of Plavix" alerting patients and doctors about Clopidogrel drug specifications metabolic disorders. Emphasis was placed on the importance and feasibility of controlling the gene detection of Clopidogrel metabolism (CYP2C19) in patients, and the corresponding antiplatelet strategy adjustment.

Chart A showed that after Clopidogrel treatment, the mortality rate of cardiovascular events and stroke in patients with CYP2C19 mutation increased by 51% compared with that in the CYP2C19 gene-wild patients.

Chart B chart showed that Clopidogrel was routinely administered after percutaneous coronary intervention. Compared with patients with wild-type CYP2C19 gene, the risk of re-embolization in patients with CYP2C19 mutation was increased by more than 2 times. Source : Jessica L.M. et al. N Eng J Med 2009, 360:354-62.

Objective: Human CYP2C19 Gene Polymorphism assay kit (PCR fluorescent probe method) is used to detect CYP2C19 gene 681, 636, and -806 loci polymorphism in vitro, and to guide Plavix (Clopidogrel Bisulfate) clinical medication.

CYP2C19 Gene alteration base Asian population probability Metabolic type *1 Wild type 65% Extensive metabolizers  *2 681G à A 20-30% Intermediate metabolizers  *3 636G à A 5-13% Poor metabolizers  *17 -806C à T 4% Ultra-rapid metabolizers    Fast Metabolism (*1/*1) 45% 1. CYP2C19 gene has no effect on Plavix efficacy. 2. Application of conventional Plavix dose ACS and PCI post-operation (75mg/d).   Intermediate Metabolism (*1/*2; *1/*3) 40% 1. Patients with a risk of thromboembolism may consider increasing the dosage. 2. Application of Plavix double dose PCI post-operation (150mg/d) from 1 week to 1 month and (75mg/d) beyond.   Slow Metabolism (*2/*2; *2/*3; *3/*3) 15% 1. Ineffective Plavix increases risk, easily leading to cardiovascular incident. 2. Consider to switch for Ticagrelor or Prasugrel. 3. PCI post-operation uses other antiplatelet drugs such as Cilostazol, change double antiplatelet therapy to triple therapy.

Ultra-fast Metabolism (*17/*17) 2% 1. Increased risk of bleeding. 2. Strengthen platelets function monitoring. c) Product Specifications   Store powder at 4°C liquid at -20°C. Store other components at 4°C. Stable for 6 months For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap.