scholarly journals . Identification of CYP2C9, VKORC1 genotypes and recommendation of warfarin dose for Vietnamese cardiovascular patients

2020 ◽  
Vol 17 (4) ◽  
pp. 589-594
Author(s):  
Nguyen Dang Ton ◽  
Nguyen Thi Thanh Hoa ◽  
Nguyen Phan Anh ◽  
Vu Phuong Nhung ◽  
Le Thi Bich Thao ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Allele Frequency ◽  
Vitamin K ◽  
Warfarin Dose ◽  
Clotting Factors ◽  
Allelic Frequencies ◽  
Cardiovascular Patients ◽  
Population Allele Frequency ◽  
Pcr Rflp ◽  
Study Population

Warfarin is a well-known anticoagulant that capable of reducing the activity of vitamin K-dependent clotting factors. It has been widely used for cardiovascular patients. However, patient’s genotype of CYP2C9 and VKORC1 remarkably affects the metabolism of warfarin. This study aims to identify the CYP2C9 and VKORC1 genotypes of 96 Vietnamese patients suffering cardiodynia or myocardial infarction and establish their daily warfarin dose. The PCR-RFLP method was used to identified the CYP2C9*2, CYP2C9*3 and VKORC1 alleles. The result indicated that allelic frequencies for CYP2C9*3 were observed at 3% of investigated patients while CYP2C9*2 alleles and genotypes were not detected in this study population. Allele frequency of VKORC1 (c. -1639G>A) was observed at 84%. Base on the CYP2C9 and VKORC1 genotypes, we recommended the daily warfarin dose for of these patients.

Effect of VKORC1 Gene Polymorphism on Warfarin Response in Razavi Khorasan Province Cardiovascular Patients

2020 ◽  
Author(s):  
Tahmine Zafari ◽  
Narges Ajilian ◽  
Atena Mansouri ◽  
Ariane Sadr-Nabav ◽  
Seyed-Alireza Esmaeili ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Warfarin Dose ◽  
International Normalized Ratio ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Present Cross Sectional Study ◽  
Cardiovascular Patients ◽  
Study Population ◽  
Polymerase Chain ◽  
Clinical Conditions

Background and Aims: Warfarin is an anticoagulant agent used for many years in treating various clinical conditions such as thromboembolisms in cardiovascular disease. Some patients require different doses of warfarin to reach the therapeutic international normalized ratio ratio. These patients have specific demographic characteristics. Genetic polymorphisms in specific genes have been reported to be an essential factor in response to warfarin. The present study investigated the effect of these polymorphisms of genes on warfarin dose necessities in pediatric of VCORC1 gene in patients. Material and Methods: Ninety-five patients with cardiovascular disease, who were receiving warfarin for at least three months, enrolled in the present cross-sectional study. Their genomic DNA was extracted from their peripheral blood, and the VKORC1 (rs9923231) polymorphism was evaluated by polymerase chain reaction and sequencing. Results: Among the study population, 48 patients (50.5%) had TC genotype and, 21 (22.1%) and 9 (9.5%) patients have TT and CC genotype, respectively. There was no significant relation between Warfarin dose and VCORC1 genotype in our population (p<0.05).  Conclusions: The VKORC1 polymorphism (rs9923231) did not significantly affect the warfarin required for cardiovascular disease patients. Further studies evaluating other genes such as CYP2C9 polymorphisms in our population are warranted.

scholarly journals Genetic Variants Of Cytochrome b-245, Alpha Polypeptide Gene And Premature Acute Myocardial Infarction Risk In An Iranian Population

2015 ◽  
Vol 34 (4) ◽  
pp. 402-408 ◽  
Author(s):  
Fatemeh Amin ◽  
Mohammad Mehdi Jahani ◽  
Hamid Ghaedi ◽  
Behnam Alipoor ◽  
Ahmad Fatemi ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Cytochrome B ◽  
Iranian Population ◽  
Pcr Rflp ◽  
Nadph Oxidase Complex ◽  
Study Population ◽  
Polymerase Chain ◽  
Artery Disease ◽  
Significant Statistical Association

SummaryBackground:Oxidative stress induced by superoxide anion plays critical roles in the pathogenesis of coronary artery disease (CAD) and hence acute myocardial infarction (AMI). The major source of superoxide production in vascular smooth muscle and endothelial cells is the NADPH oxidase complex. An essential component of this complex is p22phox, that is encoded by the cytochrome b-245, alpha polypeptide (CYBA) gene. The aim of this study was to investigate the association of CYBA variants (rs1049255 and rs4673) and premature acute myocardial infarction risk in an Iranian population.Methods:The study population consisted of 158 patients under the age of 50 years, with a diagnosis of premature AMI, and 168 age-matched controls with normal coronary angiograms. Genotyping of the polymorphisms was performed by the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP).Results:There was no association between the genotypes and allele frequencies of rs4673 polymorphism and premature acute myocardial infarction (P>0.05). A significant statistical association was observed between the genotypes distribution of rs1049255 polymorphism and AMI risk (P=0.037). Furthermore, the distribution of AA+AG/GG genotypes was found to be statistically significant between the two groups (P=0.011).Conclusions:Our findings indicated that rs1049255 but not rs4673 polymorphism is associated with premature AMI.

Association of CYP2D6*4 gene polymorphism with early papillary thyroid carcinoma

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Aynur Dağlar Aday ◽  
Tülin Öztürk ◽  
Başak Akadam Teker ◽  
Figen Aksoy ◽  
Hülya Yılmaz Aydoğan ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Allele Frequency ◽  
Papillary Thyroid ◽  
Poor Metabolizer ◽  
Tumor Stages ◽  
Pcr Rflp ◽  
Study Population ◽  
Polymerase Chain ◽  
Control Study

Abstract Objectives CYP2D6 is highly polymorphic and a common variant CYP2D6*4 results in the generation of poor metabolizer enzyme. The CYP2D6*4 variant has been associated with altered susceptibility to several cancers. The aim of the present case-control study aims to investigate the association between CYP2D6*4 polymorphism and the risk of papillary thyroid carcinoma (PTC). Materials and methods A study population of 97 cases with PTC and 120 controls were included in the study. Genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to detect the presence of CYP2D6*4. Results The CYP2D6*4 was associated with significantly increased PTC risk when compared with controls (odds ratio [OR]=1.995, 95% confidence interval [CI]=1.060–3.752, p=0.031). Besides, CYP2D6*4 allele frequency was higher in PTC patients with age ≤50 years when compared to those with age >50 (OR=2.380, 95% CI=1.191–4.755, p=0.013). CYP2D6*4 allele frequency was higher in patients who had encapsulated tumors, but it was not statistically significant (p=0.111). No relationship was found between CYP2D6*4 and PTC variants or between early (I/II) and late (III/IV) tumor stages. Conclusions Our findings indicate that the poor metabolizer CYP2D6*4 genotype may be a risk factor, especially in early PTC development. Further research with larger groups is required for the confirmation of our consequences.

Hypercoagulable State in the Watanabe Heritable Hyperlipidemic Rabbit, an Animal Model for the Progression of Atherosclerosis

1989 ◽  
Vol 61 (01) ◽  
pp. 140-143 ◽  
Author(s):  
Yoshitaka Mori ◽  
Hideo Wada ◽  
Yutaka Nagano ◽  
Katsumi Deguch ◽  
Toru Kita ◽  
...  
Keyword(s):  
Vitamin K ◽  
Fibrinogen Level ◽  
Plasma Cholesterol ◽  
Age Groups ◽  
Clotting Factor ◽  
Clotting Factors ◽  
Group A ◽  
Hyperlipidemic Rabbit ◽  
Group B ◽  
Progression Of Atherosclerosis

SummaryBlood coagulation in a strain of rabbits designated as Watanabe heritable hyperlipidemic (WHHL) rabbits was examined. The activities of vitamin K-dependent clotting factors, contact factors and clotting factor VIII (F VIII) and the fibrinogen level were significantly higher in WHHL rabbits than in normolipidemic rabbits (all age groups). Values for vitamin Independent clotting factor were already higher at 2 months of age. Contact factors and fibrinogen levels increased age after 5 to 8 months. F VIII increased between 5 and 8 months and then decreased. At 2 months of age, WHHL rabbits were divided into two groups. Group A was fed standard rabbit chow and group B standard rabbit chow containing 1% probucol. Probucol prevented the progression of atherosclerosis in group B in the absence of a significant reduction in plasma cholesterol level. F VIII and fibrinogen levels were statistically decreased in all rabbits at all ages in group B (P<0.05). These differences in clotting factors between the two groups were most obvious at 8 months (P<0.02).We conclude that vitamin K-dependent clotting factors may increase with hyperlipemia and that increases in F VIII and fibrinogen may be closely related to the progression of throm- boatherosclerosis.

Mutations which Introduce Free Cysteine Residues in the Gla-Domain of Vitamin K Dependent Proteins Result in the Formation of Complexes with α1-Microglobulin

1996 ◽  
Vol 75 (01) ◽  
pp. 070-075 ◽  
Author(s):  
E G C Wojcik ◽  
P Simioni ◽  
M v d Berg ◽  
A Girolami ◽  
R M Bertina
Keyword(s):  
Vitamin K ◽  
Protein C ◽  
Cysteine Residue ◽  
Factor Ix ◽  
Disulphide Bond ◽  
Clotting Factors ◽  
High Molecular Weight Complex ◽  
Low Concentrations ◽  
Gla Domain ◽  
Formation Of Complexes

SummaryWe have previously described a genetic factor IX variant (Cys18→Arg) for which we demonstrated that it had formed a heterodimer with armicroglobulin through formation of a disulphide bond with the remaining free cysteine residue of the disrupted disulphide bond in the Gla-domain of factor IX. Recently, we observed a similar high molecular weight complex for a genetic protein C variant (Arg-1→Cys). Both the factor IX and the protein C variants have a defect in the calcium induced conformation. In this study we show that the aminoterminus of this protein C variant is prolonged with one amino acid, cysteine. This protein C variant, as well as protein C variants with Arg9→Cys and Ser12→Cys mutations which also carry a free cysteine residue, are shown to be present in plasma as a complex with α1-microglobulin. A prothrombin variant with a Tyr44→Cys mutation, had not formed such a complex. Furthermore, complexes between normal vitamin K-dependent clotting factors and α1-microglobulin were shown to be present in plasma at low concentrations. The data suggest that the presence of an unpaired cysteine residue in the propeptide or the N-terminal half of the Gla-domain has strongly promoted the formation of a complex with α1-microglobulin in the variants.

Kinetic Aspects of the Interaction of Blood-Clotting Enzymes

1968 ◽  
Vol 20 (01/02) ◽  
pp. 078-087 ◽  
Author(s):  
H. C Hemker ◽  
A. D Muller
Keyword(s):  
Vitamin K ◽  
Blood Clotting ◽  
Experimental Results ◽  
Factor X ◽  
Clotting Factors ◽  
Vitamin K Deficiency ◽  
K Deficiency

SummaryPIVKA, the circulating anticoagulant protein found in vitamin K deficiency can, on kinetical grounds, be recognized as an analogue of factor X. The existence of analogues of other vitamin K-dependent clotting factors cannot be ruled out, but need not be assumed to explain the experimental results.

The Reaction of Thiol Compounds with the Vitamin-K Dependent Clotting Factors

1969 ◽  
Vol 21 (03) ◽  
pp. 573-579 ◽  
Author(s):  
P Fantl
Keyword(s):  
Prothrombin Time ◽  
Vitamin K ◽  
Anaerobic Conditions ◽  
Clotting Factors ◽  
Thiol Compounds ◽  
Aerobic Conditions ◽  
One Stage ◽  
Factor Ii ◽  
Ph Dependent ◽  
The One

SummaryTreatment of human and dog oxalated plasma with 0.2 to 1.0 × 10−1 M 2.3-dithiopropanol (BAL) or dithiothreitol (DTT) at 2–4° C for 30 min results in the reduction of the vitamin-K dependent clotting factors II, VII, IX and X to the respective-SH derivatives. The reaction is pH dependent. Under aerobic conditions the delayed one stage prothrombin time can be partly reversed. Under anaerobic conditions a gradual prolongation of the one stage prothrombin time occurs without reversal.In very diluted plasma treated with the dithiols, prothrombin can be converted into thrombin if serum as source of active factors VII and X is added. In contrast SH factors VII, IX and X are inactive in the specific tests. Reoxidation to active factors II, VII, IX and X takes place during adsorption and elution of the SH derivatives. The experiments have indicated that not only factor II but also factors VII, IX and X have active-S-S-centres.

Increased Activity of Vitamin K-Dependent Clotting Factors in Human Hyperlipoproteinaemia – Association with Cholesterol and Triglyceride Levels

1977 ◽  
Vol 38 (02) ◽  
pp. 0465-0474 ◽  
Author(s):  
M Constantino ◽  
C Merskey ◽  
D. J Kudzma ◽  
M. B Zucker
Keyword(s):  
Vitamin K ◽  
Plasma Lipids ◽  
Coagulation Factors ◽  
Clotting Factor ◽  
Factor X ◽  
Clotting Factors ◽  
Blood Coagulation Factors ◽  
Cholesterol Levels ◽  
Type V ◽  
Increased Activity

SummaryLevels of blood coagulation factors, cholesterol and triglyceride were measured in human plasma. Prothrombin was significantly elevated in type Ha hyperlipidaemia; prothrombin and factors VII, IX and X in type lib; and prothrombin and factors VII and IX in type V. Multiple regression analysis showed significant correlation between the levels of these plasma lipids and the vitamin K-dependent clotting factors (prothrombin, factors VII, IX and X). Higher cholesterol levels were associated with higher levels of prothrombin and factor X while higher triglyceride levels were associated with higher levels of these as well as factors VII and IX. Prothrombin showed a significant cholesterol-triglyceride interaction in that higher cholesterol levels were associated with higher prothrombin levels at all levels of triglyceride, with the most marked effects in subjects with higher triglyceride levels. Higher prothrombin levels were noted in subjects with high or moderately elevated (but not low) cholesterol levels. Ultracentrifugation of plasma in a density of 1.21 showed activity for prothrombin and factors VII and X only in the lipoprotein-free subnatant fraction. Thus, a true increase in clotting factor protein was probably present. The significance of the correlation between levels of vitamin K-dependent clotting factors and plasma lipids remains to be determined.

Comparison of Standard and Derived 12-Lead Electrocardiograms Registrated by a Simplified 3-Lead Setting with Four Electrodes for Diagnosis of Coronary Angioplasty-induced Myocardial Ischaemia

2012 ◽  
Vol 8 (3) ◽  
pp. 179 ◽  
Author(s):  
Klaus Bonaventura ◽  
Ernst Wellnhofer ◽  
Eckart Fleck ◽  
◽  
◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Myocardial Ischaemia ◽  
Coronary Angioplasty ◽  
Patient Monitoring ◽  
Percutaneous Transluminal Coronary Angioplasty ◽  
Myocardial Infarction Patient ◽  
Cardiovascular Patients ◽  
Transluminal Coronary Angioplasty ◽  
Percutaneous Transluminal ◽  
Four Electrodes

Electrocardiograms (ECGs), myocardial infarction, patient monitoring, EASI lead ECG, percutaneous transluminal coronary angioplasty, four electrodes set 12-lead ECG, 12-lead ECG, cardiovascular patients

scholarly journals Vitamin K-dependent protein S is similar to rat androgen-binding protein

1987 ◽  
Vol 243 (1) ◽  
pp. 293-296 ◽  
Author(s):  
M E Baker ◽  
F S French ◽  
D R Joseph
Keyword(s):  
Vitamin K ◽  
Binding Protein ◽  
Protein A ◽  
Serine Proteinase ◽  
Protein S ◽  
Clotting Factors ◽  
The Family ◽  
Androgen Binding Protein ◽  
Dependent Protein ◽  
Androgen Binding

Vitamin K-dependent protein S belongs to the family of clotting factors (e.g. Factors IX and X, and protein C). Unlike the other clotting factors, the C-terminal half (residues 250-634) of protein S is not a serine proteinase. In fact, the function of residues 250-634 of protein S is unknown. By using computer programs designed to detect evolutionary relationships between proteins, we find that this part of protein S is similar to rat androgen-binding protein, a protein produced and secreted by testicular Sertoli cells. The homology between protein S and androgen-binding protein suggests new approaches for elucidating their functions.

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