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Impact of Cytochrome P450 2C19* 2 and * 3 on Clopidogrel Loading Dose in Saudi Patients with Acute Coronary Syndrome

View Article: PubMed Central - PubMed

ABSTRACT

Background: Emerging evidence shows that clopidogrel is greatly affected by non-functioning alleles measured by P2Y12 or platelet reactivity units (PRU). Cardiac events during short in-hospital stays have been inconclusively suggested as the main causes of discrepancies.

Objectives: Evaluate the impact of CYP2C19 allele * 2 and allele * 3 on PRU and the potential clinical consequences of such interaction. To establish a rough estimation for the safe PRU limits for short in-hospital stay following PCI.

Method: A short-term experimental study was conducted with 90 patients who underwent coronary angioplasty with drug eluting stents at the Prince Sultan Cardiac Center, Buraidah. All the patients received an initial loading dose of 300 mg clopidogrel, followed by 75 mg daily. Blood samples were used for DNA extraction for cytochrome P450 (CYP) and real-time polymerase chain reaction (PCR) was used for genotyping. PRU and inhibition rate were tested by Verifynow®. All in-hospital cardiac events were recorded until patients were discharged.

Results: Genotypes 1/1, 2/2, and 1/2 were expressed by 60, 28, and two patients (67, 32, and 3%), respectively. The 
PRU of the female patients was significantly higher than that of the male patients was (255.6 ± 68.8 and 177.7 ± 66.6, 
p = 0.000, respectively). There was no significant difference in PRUs (193 ± 79 and 212 ±55.4, respectively, p = 0.349), nor inhibition (17.9 ± 18.80 and 13.88 ± 11.5, p = 0.135) in wild and resistant variants, respectively. We only reported one cardiac in-thrombosis events.

Conclusion: Genotype differences may not explain variations in the PRU of patients during short-term in-hospital stays. Although it is difficult to confirm, 117–267 units may be a safe PRU range for such patients, with emphasis on attaining higher PRU values in females.

No MeSH data available.


Real-Time PCR.
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Figure 1: Real-Time PCR.

Mentions: The positive control human DNA CYP2C19* 2 and * 3, wild type, and heterozygous were all diluted 1:4. A negative control was also included for each run. The reproducibility was tested by analyzing nine random samples 10 times each (three of each wild/wild, wild/mutant and mutant/mutant). The mix and DNA for each sample were pipetted into the LightCycler capillaries, which were sealed, centrifuged using the LightCycler carousel centrifuge, and then placed into the LightCycler instrument. The denaturation, melting, and renaturation processes are shown in Fig. 1. The gradual increase should allow for monitoring the decline in fluorescence of the melting hybrids as a function of temperature. Fluorescence curves were analyzed using the LightCycler software (version 3.5.3)


Impact of Cytochrome P450 2C19* 2 and * 3 on Clopidogrel Loading Dose in Saudi Patients with Acute Coronary Syndrome
Real-Time PCR.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4997918&req=5

Figure 1: Real-Time PCR.
Mentions: The positive control human DNA CYP2C19* 2 and * 3, wild type, and heterozygous were all diluted 1:4. A negative control was also included for each run. The reproducibility was tested by analyzing nine random samples 10 times each (three of each wild/wild, wild/mutant and mutant/mutant). The mix and DNA for each sample were pipetted into the LightCycler capillaries, which were sealed, centrifuged using the LightCycler carousel centrifuge, and then placed into the LightCycler instrument. The denaturation, melting, and renaturation processes are shown in Fig. 1. The gradual increase should allow for monitoring the decline in fluorescence of the melting hybrids as a function of temperature. Fluorescence curves were analyzed using the LightCycler software (version 3.5.3)

View Article: PubMed Central - PubMed

ABSTRACT

Background: Emerging evidence shows that clopidogrel is greatly affected by non-functioning alleles measured by P2Y12 or platelet reactivity units (PRU). Cardiac events during short in-hospital stays have been inconclusively suggested as the main causes of discrepancies.

Objectives: Evaluate the impact of CYP2C19 allele * 2 and allele * 3 on PRU and the potential clinical consequences of such interaction. To establish a rough estimation for the safe PRU limits for short in-hospital stay following PCI.

Method: A short-term experimental study was conducted with 90 patients who underwent coronary angioplasty with drug eluting stents at the Prince Sultan Cardiac Center, Buraidah. All the patients received an initial loading dose of 300 mg clopidogrel, followed by 75 mg daily. Blood samples were used for DNA extraction for cytochrome P450 (CYP) and real-time polymerase chain reaction (PCR) was used for genotyping. PRU and inhibition rate were tested by Verifynow®. All in-hospital cardiac events were recorded until patients were discharged.

Results: Genotypes 1/1, 2/2, and 1/2 were expressed by 60, 28, and two patients (67, 32, and 3%), respectively. The 
PRU of the female patients was significantly higher than that of the male patients was (255.6 ± 68.8 and 177.7 ± 66.6, 
p = 0.000, respectively). There was no significant difference in PRUs (193 ± 79 and 212 ±55.4, respectively, p = 0.349), nor inhibition (17.9 ± 18.80 and 13.88 ± 11.5, p = 0.135) in wild and resistant variants, respectively. We only reported one cardiac in-thrombosis events.

Conclusion: Genotype differences may not explain variations in the PRU of patients during short-term in-hospital stays. Although it is difficult to confirm, 117–267 units may be a safe PRU range for such patients, with emphasis on attaining higher PRU values in females.

No MeSH data available.