Warfarin dose requirement with different genotypes of polymorphisms on CYP2C9 and VKORC1 and indications in Han-Chinese patients

2017 ◽  
Vol 55 (02) ◽  
pp. 126-132 ◽  
Author(s):  
Weirong Chen ◽  
Luhua Wu ◽  
Xin Liu ◽  
Yue Shen ◽  
Yan Liang ◽  
...  
Keyword(s):  
Warfarin Dose ◽  
Han Chinese ◽  
Chinese Patients ◽  
Dose Requirement ◽  
Warfarin Dose Requirement

Genetic polymorphism in exon 4 of cytochrome P450 CYP2C9 may be associated with warfarin sensitivity in Chinese patients

Blood ◽  
2001 ◽  
Vol 98 (8) ◽  
pp. 2584-2587 ◽  
Author(s):  
Anskar Y. H. Leung ◽  
Howard C. H. Chow ◽  
Y. L. Kwong ◽  
Albert K. W. Lie ◽  
Alvin T. K. Fung ◽  
...  
Keyword(s):  
Direct Sequencing ◽  
Warfarin Dose ◽  
Interindividual Variation ◽  
Chinese Patients ◽  
Chain Reaction ◽  
Dose Requirement ◽  
Warfarin Dose Requirement ◽  
The Common ◽  
Polymerase Chain ◽  
Exon 4

Abstract CYP2C9 polymorphisms reported in Caucasians (Arg144Cys in exon 3 and Ile359Leu in exon 7) are extremely uncommon in Chinese persons. The genotype of CYP2C9 in this population was characterized to investigate its relation with the interindividual variation in warfarin dosages. Eighty-nine Chinese patients receiving warfarin were recruited. Target sequences inCYP2C9 in exons 1, 4, and 5 were amplified by polymerase chain reaction, followed by direct sequencing. Polymorphisms at 4 positions were demonstrated in exon 4. Heterozygosities for 608TTG>GTG (Leu208Val), 561CAG>CCG (Gln192Pro), 537CAT>CCT (His184Pro), and 527ATT>CTT (Ile181Leu) existed at frequencies 0.75, 0.20, 0.10, and 0.09, respectively. Seventeen patients (frequency, 0.19) were homozygous for Val208. The common genotypic combinations at these loci are Ile181/His184/Gln192/Leu208Val (n = 50), Ile181/His184/Gln192/Val208 (n = 15), Ile181/His184/Gln192/Leu208 (n = 4), Ile181/His184/Gln192Pro/Leu208Val (n = 6), Ile181/His184Pro/Gln192Pro/Leu208Val (n = 4), and Ile181Leu/His184/Gln192Pro/ Leu208Val (n = 4). At codon 208, heterozygous Leu208Val and homozygous Val208 appeared to have a lower warfarin dose requirement than the homozygous Leu208. Patients who are heterozygous for Ile181Leu had a higher warfarin dose requirement than the homozygous Ile181. Amplified sequences in exons 1 and 5 did not exhibit polymorphism. In conclusion, Chinese patients showed genetic polymorphisms of CYP2C9 in exon 4 and at codon 208; most were heterozygous Leu208Val and homozygous Val208. Homozygous Leu208, a common allele in Caucasians, is uncommon in this cohort. The significance of these CYP2C9 polymorphic alleles remains to be determined.

Association between polymorphisms in microRNA seed region and warfarin stable dose

2020 ◽  
pp. postgradmedj-2019-137197
Author(s):  
Maryam Hosseindokht ◽  
Hamed Zare ◽  
Rasoul Salehi ◽  
Leyla Pourgholi ◽  
Shayan Ziaee ◽  
...  
Keyword(s):  
Fragment Length Polymorphism ◽  
Interindividual Variability ◽  
Warfarin Dose ◽  
Optimal Dose ◽  
Seed Region ◽  
Dose Requirement ◽  
Vitamin K Cycle ◽  
Warfarin Dose Requirement ◽  
Potential Factor ◽  
Warfarin Maintenance Dose

BackgroundThe optimal dose of anticoagulant warfarin varies among patients to achieve the target international normalised ratio. Although genetic variations related to warfarin pharmacokinetics and vitamin K cycle are important factors associated with warfarin dose requirements, these variations do not completely explain the large interindividual variability observed in the most populations, suggesting that additional factors may contribute to this variability. microRNAs have recently been introduced as regulators of drug function genes, and therefore, may be involved in drug responses. In this study, we aimed to evaluate the possible association between variants in the seed region of microRNAs, which target the genes involved in the action of warfarin and warfarin dose requirement.Methods526 samples were collected from Iranian patients. Four selected polymorphisms in the seed region of microRNAs (rs2910164, rs66683138, rs12416605 and rs35770269 in miR-146a, miR-3622a, miR-938 and miR-449c, respectively) were genotyped by PCR-restriction fragment length polymorphism method.Resultsrs2910164 C/G in the seed region of miR-146a was associated with warfarin dose requirement (p<0.001); the patients with GG genotype had the higher mean dose of warfarin (40.6 mg/week, compared with 33.9 and 31.8 mg/week for GC and CC genotypes, respectively). The association of other polymorphisms with warfarin dose requirement was not statistically significant.Conclusionrs2910164 C/G in the seed region of miR-146a is associated with warfarin maintenance dose, likely by disrupting interaction between miR-146a and ATP-binding cassette subfamily B member 1 gene, ABCB1. Therefore, this polymorphism may possibly be a potential factor for assessment of warfarin dose requirements.

The effects of CYP2C9 and VKORC1 gene polymorphisms on warfarin maintenance dose in Turkish cardiac patients

2020 ◽  
Author(s):  
Cansu Selcan Akdeniz ◽  
Mehtap Cevik ◽  
Ismail Polat Canbolat ◽  
Selen Yurdakul ◽  
Penbe Cagatay ◽  
...  
Keyword(s):  
Warfarin Dose ◽  
Individual Variability ◽  
Considerable Proportion ◽  
Wild Type ◽  
Dose Requirement ◽  
Study Results ◽  
Warfarin Dose Requirement ◽  
Turkish Patients ◽  
Vkorc1 Gene ◽  
Warfarin Maintenance Dose

Aim: Our aim was to examine the effect of CYP2C9 and VKORC1 polymorphisms on warfarin dose requirements in Turkish patients. Materials & methods: 24 warfarin prescribed patients were included and analyzed for eight VKORC1 and 6 CYP2C9 polymorphisms in the study. Results: Patients with CYP2C9 *1/*1 and VKORC1 -1639 GG and GA genotypes required higher warfarin doses in comparison to wild type VKORC1 genotype. Patients with CYP2C9 *1/*3 and VKORC1 -1639 GG genotypes simultaneously, required the lowest dose of warfarin (4.64 mg/day). Patients with CYP2C9 *1/*1 and VKORC1 9041 AA genotype were found to require higher warfarin doses. Conclusion: Our results provide additional evidence to support the hypothesis that CYP2C9 *2, *3, VKORC1 9041 G > A polymorphisms explain considerable proportion of inter-individual variability in warfarin dose requirement.

scholarly journals Vitamin K antagonists in children with heart disease: height and VKORC1 genotype are the main determinants of the warfarin dose requirement

Blood ◽  
2012 ◽  
Vol 119 (3) ◽  
pp. 861-867 ◽  
Author(s):  
Caroline Moreau ◽  
Fanny Bajolle ◽  
Virginie Siguret ◽  
Dominique Lasne ◽  
Jean-Louis Golmard ◽  
...  
Keyword(s):  
Vitamin K ◽  
Dose Response ◽  
Maintenance Dose ◽  
Vitamin K Antagonists ◽  
Warfarin Dose ◽  
International Normalized Ratio ◽  
Individual Variability ◽  
Dose Requirement ◽  
Warfarin Dose Requirement ◽  
Main Determinants

Abstract Managing vitamin K antagonist (VKA) therapy is challenging in children because of a narrow therapeutic range and wide inter- and intra-individual variability in dose response. Only a few small studies have investigated the effect of nongenetic and genetic factors on the dose response to VKAs in children. In a cohort study including 118 children (median age 9 years; range, 3 months-18 years) mostly with cardiac disease, we evaluated by multivariate analysis the relative contribution of nongenetic factors and VKORC1/CYP2C9/CYP4F2 genotypes on warfarin (n = 83) or fluindione (n = 35) maintenance dose and the influence of these factors on the time spent within/above/below the range. The results showed that height, target international normalized ratio and VKORC1 and CYP2C9 genotypes were the main determinants of warfarin dose requirement, accounting for 48.1%, 4.4%, 18.2%, and 2.0% of variability, respectively, and explaining 69.7% of the variability. Our model predicted the warfarin dose within 7 mg/wk in 86.7% of patients. None of the covariates was associated with the time spent above or below the international normalized ratio range. Whether this model predicts accurately the effective maintenance dose is currently being investigated.

scholarly journals Warfarin dose requirement in patients having severe thrombosis or thrombophilia

2019 ◽  
Vol 85 (8) ◽  
pp. 1684-1691 ◽  
Author(s):  
Tuukka A. Helin ◽  
Lotta Joutsi‐Korhonen ◽  
Heidi Asmundela ◽  
Mikko Niemi ◽  
Arto Orpana ◽  
...  
Keyword(s):  
Warfarin Dose ◽  
Dose Requirement ◽  
Warfarin Dose Requirement
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