The effect of GGCX and CYP4F2 gene polymorphisms in genotype-guided dosing of warfarin in patients with a history of cardiac surgery

Azarara, Maryam; Afrasibirad, Abbas; Farzamikia, Negin; Alijani, Aylar; Sakhinia, Ebrahim

doi:10.1007/s40005-016-0295-3

Cited by 4 publications

(5 citation statements)

References 26 publications

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“…These data suggested the bioavailability in humans can be increased compared to that in rats. In addition, the differences between human and rat might be caused by the genomic differences of cytochrome P450 genes between human and rodent [25,26].…”

Section: Discussionmentioning

confidence: 99%

In vitro and in vivo pharmacokinetic characterization of LMT-28 as a novel small molecular interleukin-6 inhibitor

Ahn

Heo

Jun

et al. 2020

Asian-Australas J Anim Sci

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Objective: Interleukin-6 (IL-6) is a T cell-derived B cell stimulating factor which plays an important role in inflammatory diseases. In this study, the pharmacokinetic properties of LMT-28 including physicochemical property, in vitro liver microsomal stability and an in vivo pharmacokinetic study using BALB/c mice were characterized.Methods: LMT-28 has been synthesized and is being developed as a novel therapeutic IL-6 inhibitor. The physicochemical properties and in vitro pharmacokinetic profiles such as liver microsomal stability and Madin-Darby canine kidney (MDCK) cell permeability assay were examined. For in vivo pharmacokinetic studies, pharmacokinetic parameters using BALB/c mice were calculated.Results: The logarithm of the partition coefficient value (LogP; 3.65) and the apparent permeability coefficient values (Papp; 9.7×10–6 cm/s) showed that LMT-28 possesses a moderate-high cell permeability property across MDCK cell monolayers. The plasma protein binding rate of LMT-28 was 92.4% and mostly bound to serum albumin. The metabolic half-life (t1/2) values of LMT-28 were 15.3 min for rat and 21.9 min for human at the concentration 1 μM. The area under the plasma drug concentration-time curve and Cmax after oral administration (5 mg/kg) of LMT-28 were 302±209 h∙ng/mL and 137±100 ng/mL, respectively.Conclusion: These data suggest that LMT-28 may have good physicochemical and pharmacokinetic properties and may be a novel oral drug candidate as the first synthetic IL-6 inhibitor to ameliorate mammalian inflammation.

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Section: Discussionmentioning

confidence: 99%

In vitro and in vivo pharmacokinetic characterization of LMT-28 as a novel small molecular interleukin-6 inhibitor

Ahn

Heo

Jun

et al. 2020

Asian-Australas J Anim Sci

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“…Genotyping polymorphisms in the VKORC1 rs9923231 (−1639G > A; VKORC1*2), CYP4F2 rs2108622 (1347C > T), and GGCX rs11676382 (12970C > G) genes was performed as previously described. [ 15 , 20 ]…”

Section: Methodsmentioning

confidence: 99%

“…Numerous studies have shown the need to adjust drug doses in patients harboring such variants. [15][16][17] Therefore, this study aimed to investigate a possible link between specific polymorphisms in the VKORC1, CYP4F2, and GGCX genes and the risk of developing a first episode of acute ischemic stroke in patients without a known embolic source. By identifying potential genetic risk factors associated with ischemic stroke, this study aimed to contribute to a better understanding of the underlying mechanisms of these events and contribute to the development of prevention strategies for at-risk individuals.…”

Section: Introductionmentioning

confidence: 99%

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Association among VKORC1 rs9923231, CYP4F2 rs2108622, GGCX rs11676382 polymorphisms and acute ischemic stroke

Iluţ,

Vesa,

Văcăraş

et al. 2023

Medicine

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Acute ischemic stroke is a major cause of morbidity and mortality worldwide, and genetic factors play a role in the risk of stroke. Single nucleotide polymorphisms (SNPs) in the VKORC1, CYP4F2, and GGCX genes have been linked to clinical outcomes, such as bleeding and cardiovascular diseases. This study aimed to investigate the association between specific polymorphisms in these genes and the risk of developing the first episode of acute ischemic stroke in patients without a known embolic source. This retrospective, cross-sectional, observational, analytical, case-control study included adult patients diagnosed with acute ischemic stroke. The SNPs in VKORC1 rs9923231, CYP4F2 rs2108622, GGCX rs11676382 genes were genotyped and analyzed together with the demographic and clinical factors of the 2 groups of patients. The presence of SNPs in VKORC1 or CYP4F2 genes significantly increased the risk of ischemic stroke in the context of smoking, arterial hypertension, and carotid plaque burden. The multivariate logistic model revealed that smoking (odds ratio [OR] = 3.920; P < .001), the presence of carotid plaques (OR = 2.661; P < .001) and low-density lipoprotein cholesterol values >77 mg/dL (OR = 2.574; P < .001) were independently associated with stroke. Polymorphisms in the VKORC1 and CYP4F2 genes may increase the risk of ischemic stroke in patients without a determined embolic source. Smoking, the presence of carotid plaques, and high low-density lipoprotein cholesterol levels were reconfirmed as important factors associated with ischemic stroke.

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“…DNA extraction was performed using a genomic DNA purification kit (Wizard Genomic DNA Purification Kit, Promega, Madison, WI, USA). Genotyping of the VKORC1 [24][25][26], CYP4F2 [27], and GGCX [27] polymorphisms was performed as previously described. VKORC1 and CYP4F2 mutational status was dichotomized between no mutation and either monoallelic or biallelic mutation.…”

Section: Methodsmentioning

confidence: 99%

CYP4F2 and VKORC1 Polymorphisms Amplify the Risk of Carotid Plaque Formation

Vesa

Vlaicu

Văcăraș

et al. 2020

Genes

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Introduction: Atherosclerosis represents the process by which fibrous plaques are formed in the arterial wall, increasing its rigidity with a subsequent decrease in blood flow which can lead to several cardiovascular events. Seeing as vitamin K antagonists are involved in the pathogenesis of atherosclerosis, we decided to investigate whether polymorphisms in genes that influence vitamin K metabolism might have an impact in modulating the risk of plaque formation. Patients and Methods: In the current study we included adult patients admitted in the Clinical Municipal Hospital of Cluj-Napoca without any carotid or femoral plaques clinically visible at the initial investigation, and a five year follow-up was subsequently performed. We recorded the following patient characteristics: age at inclusion, gender, area of living, smoking, presence of carotid and/or femoral plaques at five years, ischemic heart disease, arterial hypertension, atrial fibrillation, heart failure, diabetes mellitus, obesity, dyslipidemia, drug (oral anticoagulants, antihypertensives, hypolipidemic, anti-diabetic) use and status for the following gene polymorphisms: VKORC1 1639 G>A, CYP4F2 1347 G>T and GGCX 12970 C>G. Results: We observed that the major predictor of both carotid and femoral plaque formation is represented by ischemic cardiac disease. VKORC1 and CYP4F2 polymorphisms did not predict plaque formation, except for VKORC1 homozygous mutants. Nonetheless, both VKORC1 and CYP4F2 interacted with ischemic cardiac disease, increasing the risk of developing a carotid plaque, while only CYP4F2, but not VKORC1, interacted with ischemic cardiac disease to increase the risk of femoral plaque formation. Conclusions: We documented that CYP4F2 and VKORC1 polymorphisms boost the proinflammatory plaque environment (observed indirectly through the presence of ischemic heart disease), increasing the risk of plaque development.

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The effect of GGCX and CYP4F2 gene polymorphisms in genotype-guided dosing of warfarin in patients with a history of cardiac surgery

Cited by 4 publications

References 26 publications

In vitro and in vivo pharmacokinetic characterization of LMT-28 as a novel small molecular interleukin-6 inhibitor

In vitro and in vivo pharmacokinetic characterization of LMT-28 as a novel small molecular interleukin-6 inhibitor

Association among VKORC1 rs9923231, CYP4F2 rs2108622, GGCX rs11676382 polymorphisms and acute ischemic stroke

CYP4F2 and VKORC1 Polymorphisms Amplify the Risk of Carotid Plaque Formation

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