Diversity of pharmacogenomic variants affecting warfarin metabolism in Sri Lankans.

Aims: To describe the diversity of pharmacogenomic variants affecting warfarin metabolism in Sri Lankans. Materials & methods: Genotype data were filtered out from an anonymized database of 400 Sri Lankans, and minor allele frequencies (MAF) were calculated. Variants of CYP2C9, VKORC1 and CYP4F2 genes were studied. Results: Overall, CYP2C9*2 and CYP2C9*3 alleles had MAFs of 2.25% (95% CI: 0.80-3.70) and 10.38% (95% CI: 7.50-13.50), respectively. CYP2C9*11 and CYP2C9*14 alleles had MAFs of 0.13% (95% CI: 0-0.74) and 2.50% (95% CI: 0.97-4.03), respectively. MAFs of VKORC1 variants rs7294, rs9934438, rs8050894 and rs2884737 were 47.25% (95% CI: 42.36-52.14), 10.13% (95% CI: 7.28-13.22), 9.88% (95% CI: 7.06-12.94) and 4.88% (95% CI: 2.86-7.14), respectively. MAF of CYP4F2 variant rs2108622 was 45.63% (95% CI: 40.87-50.63). Conclusion: Compared with other populations, the frequencies of some studied variants were significantly different in Sri Lankans, and these are likely to account for variability in warfarin dosage requirements.

[1]  S. Kimmel,et al.  Genetic Factors Influencing Warfarin Dose in Black‐African Patients: A Systematic Review and Meta‐Analysis , 2019, Clinical pharmacology and therapeutics.

[2]  A. Kocael,et al.  Interpretation of the effect of CYP2C9, VKORC1 and CYP4F2 variants on warfarin dosing adjustment in Turkey , 2019, Molecular Biology Reports.

[3]  S. Wong,et al.  Genotype‐guided warfarin dosing vs. conventional dosing strategies: a systematic review and meta‐analysis of randomized controlled trials , 2018, British journal of clinical pharmacology.

[4]  P. C. Santos,et al.  Genotype-guided warfarin therapy: current status. , 2018, Pharmacogenomics.

[5]  J. Indrakumar New oral anticoagulants in clinical practice – time to replace warfarin? , 2017 .

[6]  T E Klein,et al.  Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Pharmacogenetics‐Guided Warfarin Dosing: 2017 Update , 2017, Clinical pharmacology and therapeutics.

[7]  G. Wang,et al.  Pharmacogenetics-Based versus Conventional Dosing of Warfarin: A Meta-Analysis of Randomized Controlled Trials , 2015, PloS one.

[8]  Y. Wang,et al.  Effect of gene polymorphims on the warfarin treatment at initial stage , 2015, The Pharmacogenomics Journal.

[9]  M. Pirmohamed,et al.  A Review of A Priori Regression Models for Warfarin Maintenance Dose Prediction , 2014, PloS one.

[10]  William K Redekop,et al.  Pharmacogenetic-guided dosing of coumarin anticoagulants: algorithms for warfarin, acenocoumarol and phenprocoumon. , 2014, British journal of clinical pharmacology.

[11]  D. Shewade,et al.  Inter and intra ethnic variation of vitamin K epoxide reductase complex and cytochrome P450 4F2 genetic polymorphisms and their prevalence in South Indian population , 2013, Indian journal of human genetics.

[12]  D. Hu,et al.  Influence of CYP4F2 genotype on warfarin dose requirement-a systematic review and meta-analysis. , 2012, Thrombosis research.

[13]  R. Desnick,et al.  Combined CYP2C9, VKORC1 and CYP4F2 frequencies among racial and ethnic groups. , 2010, Pharmacogenomics.

[14]  M. Rieder,et al.  CYP4F2 Is a Vitamin K1 Oxidase: An Explanation for Altered Warfarin Dose in Carriers of the V433M Variant , 2009, Molecular Pharmacology.

[15]  Russ B. Altman,et al.  PharmGKB and the International Warfarin Pharmacogenetics Consortium: the changing role for pharmacogenomic databases and single‐drug pharmacogenetics , 2008, Human mutation.

[16]  A. Wittkowsky Warfarin and Other Coumarin Derivatives: Pharmacokinetics, Pharmacodynamics, and Drug Interactions , 2003, Seminars in vascular medicine.

[17]  H. Echizen,et al.  Pharmacogenetics of Warfarin Elimination and its Clinical Implications , 2001, Clinical pharmacokinetics.

[18]  S. Ham,et al.  MECHANISM of action of vitamin K. , 1956, Nutrition reviews.