Warfarin dose and INR related to genotypes of CYP2C9 and VKORC1 in patients with myocardial infarction

Haug, Kari Bente Foss; Sharikabad, Mohammad Nouri; Kringen, Marianne Kristiansen; Narum, Sigrid; Sjaatil, Stine T; Johansen, Per Wiik; Kierulf, Peter; Seljeflot, Ingebjørg; Arnesen, Harald; Brørs, Odd

doi:10.1186/1477-9560-6-7

Cited by 17 publications

(13 citation statements)

References 31 publications

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“…In agreement with our results, Haug et al [18] reported that 40.1% of their patients who treated with warfarin for the primary indication of myocardial infarction showed wild VKORC1 (G/G), whereas 46.7% had heterozygous genotype and 13.2% showed the homozygous genotype. Similarly, Tatarū nas et al [19] studied optimal warfarin doses after heart valve replacement and found that 38.6% showed the wild genotype, whereas 54.2 and 7.2% showed the heterozygous and homozygous genotypes, respectively.…”

Section: Discussionsupporting

confidence: 95%

“…This is in line with Haug et al [18] who reported that frequencies of CYP2C9 Ã 1/ Ã 1, CYP2C9 Ã 1/ Ã 2 and CYP2C9 Ã 2/ Ã 2 were 63, 18 and 2%, respectively, whereas no mutation was detected regarding the distribution of CYP2C9 Ã 1/ Ã 3, CYP2C9 Ã 2/ Ã 3 and CYP2C9 Ã 3/ Ã 3 genotypes. Tatarū nas et al [19] also reported nearly similar frequencies wherein CYP2C9 Ã 1/ Ã 1 was 66.3%, 20.5% for the CYP2C9 Ã 1/ Ã 2 genotype, whereas 3.6, 8.4 and 1.2% for CYP2C9 Ã 2/ Ã 2, CYP2C9 Ã 1/ Ã 3, CYP2C9 Ã 2/ Ã 3 genotypes, respectively, with no mutation regarding CYP2C9 Ã 3/ Ã 3 genotype.…”

Section: Discussionsupporting

confidence: 94%

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Impact of CYP2C9 and VKORC1 genetic polymorphisms upon warfarin dose requirements in Egyptian patients with acute coronary syndrome

Ghozlan

Foad²,

Darwish³

et al. 2015

Blood Coagulation &Amp; Fibrinolysis

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Warfarin is the most widely prescribed anticoagulant drugs. Cytochrome P450-2C9 (CYP2C9) and vitamin K epoxide reductase-oxidaxe complex subunit 1 (VKORC1) contribute significantly to the variability of warfarin dose requirements among patients. We investigated the impact of CYP2C9 and VKORC1 polymorphisms on the variability of warfarin dosage requirements in Egyptian patients with acute coronary syndrome and their association with other nongenetic factors. Eighty participants with acute coronary syndrome were enrolled in this cross-sectional study. Associations between CYP2C9 and VKORC1 gene variants together with daily warfarin dose, demographic data, clinical status of patients and time to target international normalized ratio were assessed. Mean warfarin dose among patients with wild-type CYP2C91/1 genotype was significantly higher than heterozygous CYP2C91/2 and CYP2C91/3 variants (P ≤ 0.001). Patients with wild VKORC1 (G/G) genotype were treated with significantly higher daily warfarin dosages than homozygous (A/A) and heterozygous (G/A) genotypes. Patients carrying VKORC1 (G/G) genotype in combination with the CYP2C91/1 type alleles had the highest daily warfarin dosage, whereas the lowest daily warfarin dosage to achieve the required clinical effect was found among patients having CYP2C91/2 and CYP2C91/3 genotypes combined with VKORC1 (A/A) genotype (P ≤ 0.001). Regression analysis revealed that age, height, CYP2C9 and VKORC1 genotypes were significantly associated with warfarin dose. Genetic polymorphisms in VKORC1, CYP2C9 along with age and height are determinants of warfarin dose requirements in Egyptian population acute coronary syndrome. Higher warfarin loading dose is required for both wild CYP2C9 and VKORC1 gene variants which may contribute to warfarin-resistant cases.

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Section: Discussionsupporting

confidence: 95%

Section: Discussionsupporting

confidence: 94%

Impact of CYP2C9 and VKORC1 genetic polymorphisms upon warfarin dose requirements in Egyptian patients with acute coronary syndrome

Ghozlan

Foad²,

Darwish³

et al. 2015

Blood Coagulation &Amp; Fibrinolysis

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“…The frequencies of the two heterozygous genotypes CYP2C9*1/*2 and CYP2C9*1/*3 were 17.8% and 11.9%, respectively, whereas compound heterozygotes of CYP2C9*2/*3 was 1.6%. Our results are consistent with those of Caucasian population which was studied by Hauge et al (2008) (24). They evaluated the genotype distributions of CYP2C9*2 and CYP2C9*3 polymorphisms in 212 patients and found that the genotype frequency of the CYP2C9*1/*2 variant was 17.9%, whereas the CYP2C9*1/*3 variant was 9.4%.…”

Section: Discussionsupporting

confidence: 92%

“…Our results suggest that VKORC1 polymorphism may have a greater effect on warfarin dose than CYP2C9 polymorphism, and this is in accordance with the findings of previous studies. RHaug et al studied 105 Norwegian patients of Caucasian race and the findings confirmed that the VKORC1 polymorphism had a larger impact (25%) compared to CYP2C9 (7%) (24). Another study by Herman et al which analyzed 165 Slovenians showed that VKORC1 contributed 34% and CYP2C9 18% (22).…”

Section: Discussionmentioning

confidence: 89%

Association between Cytochrome P450 2 C9 and Vitamin K Epoxide Reductase Complex Subunit 1 Polymorphisms with Warfarin dose among Iranian Patients

et al. 2016

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Background: Warfarin is a common anticoagulant drug that has a narrow therapeutic index; higher dose causes excessive bleeding and lower dose leads to cerebrovascular clotting and stroke in patients. Genetic factors that have been associated with warfarin response are the genes of cytochrome P450 2C9 (CYP2C9), which metabolize the more active S-enantiomer of warfarin, and vitamin K epoxide reductase (VKOR), the target site for warfarin. The present study was conducted to investigate the association between CYP2C9*2, CYP2C9*3 and VKORC1 (-1639 G>A) polymorphisms with warfarin daily dose on 118 Iranian patients under warfarin treatment. Materials and Methods: This study is comprised of 118 Iranian patients on warfarin treatment who attended the PT Clinic. Genotyping of CYP2C9*2, CYP2C9*3 and VKORC1 (-1639 G>A) was performed by PCR-RFLP method. Multiple regression model was performed for statistical analyses and P<0.05 was considered as significance level. Results: The allelic frequencies of CYP2C9*2 and CYP2C9*3 were 19% and 7%, respectively. Patients with ≥1 CYP2C9 variant allele had a significantly lower mean warfarin daily dose compared with patients with the wild-type genotype. The allelic frequencies of VKORC1 were 14.4%, 57.6% and 27.9% for GG, GA, and AA genotypes, respectively. The mean (SD) warfarin daily dose in patients with the VKORC1 (-1639) GG genotype was significantly higher than GA and AA patients. Conclusion: CYP2C9*2, CYP2C9*3 and VKORC1 (-1639 G>A) polymorphisms had significant association with warfarin daily dose. Furthermore, the daily warfarin dose was not influenced by age, height, weight and sex.

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“…The simplicity and speed of this assay makes it feasible for point of care testing. 30,31 Single hybridization probes can be used on any LightCycler, although the fluorescence to background ratio is less than with dual hybridization probes.…”

Section: Reducing Complexitymentioning

confidence: 99%

LightCycler Technology in Molecular Diagnostics

Lyon

Wittwer

2009

The Journal of Molecular Diagnostics

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From the first report of the LightCycler as a real-time polymerase chain reaction (PCR) instrument 1 clinical laboratories quickly realized its potential as a diagnostic tool. Quantitative applications important for infectious disease and oncology applications were followed by genotyping assays that took advantage of accurate temperature control to melt DNA amplicons or probe/amplicon duplexes. The first Food and Drug Administration-cleared molecular genetic assays were developed for this platform, specifically genotyping single base variants in F5 and F2. According to a College of American Pathologists survey, 2 ϳ30% of clinical laboratories report using the LightCycler for these two assays. This article will review the history of LightCycler technology, focusing on those applications widely incorporated into molecular diagnostics. In addition we will review recent developments that may impact future clinical testing.Real-time PCR instruments simultaneously amplify and detect, eliminating the need to open tubes containing PCR amplicon and therefore reducing the risk of future contamination. Fluorescent dyes or probes allow continuous monitoring as template DNA is amplified.3 By monitoring fluorescence every cycle, the amount of original target can be calculated. By monitoring fluorescence as the temperature changes, genotyping and heterozygote scanning can be performed by melting analysis, often removing the need for downstream analysis.The first two platforms developed for real-time PCR were the LightCycler (Roche, Indianapolis, IN) and the ABI 7700 (Applied Biosystems, Foster City, CA). The instruments were as different as the groups that created them. At the time, ABI was the undisputed corporate leader of PCR technology and the 7700 was a large 96-well laser-based instrument focused on throughput.

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Warfarin dose and INR related to genotypes of CYP2C9 and VKORC1 in patients with myocardial infarction

Abstract: CYP2C9 and VKORC1 genotype frequencies in myocardial infarction patients appear similar to other patient groups and have similar impact on warfarin maintenance dose.

Cited by 17 publications

References 31 publications

Impact of CYP2C9 and VKORC1 genetic polymorphisms upon warfarin dose requirements in Egyptian patients with acute coronary syndrome

Impact of CYP2C9 and VKORC1 genetic polymorphisms upon warfarin dose requirements in Egyptian patients with acute coronary syndrome

Association between Cytochrome P450 2 C9 and Vitamin K Epoxide Reductase Complex Subunit 1 Polymorphisms with Warfarin dose among Iranian Patients

LightCycler Technology in Molecular Diagnostics

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