Diversity of pharmacogenomic variants affecting warfarin metabolism in Sri Lankans

Pharmacogenomics. 2022 Nov;23(17):917-923. doi: 10.2217/pgs-2022-0026. Epub 2022 Oct 26.

Abstract

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.

Keywords: CYP2C9; CYP4F2; Sri Lanka; VKORC1; pharmacogenomics; warfarin.

MeSH terms

  • Anticoagulants
  • Cytochrome P-450 CYP2C9 / genetics
  • Cytochrome P450 Family 4 / genetics
  • Dose-Response Relationship, Drug
  • Genotype
  • Humans
  • Pharmacogenomic Variants*
  • Sri Lanka
  • Vitamin K Epoxide Reductases / genetics
  • Warfarin*

Substances

  • Warfarin
  • Vitamin K Epoxide Reductases
  • Cytochrome P-450 CYP2C9
  • Cytochrome P450 Family 4
  • Anticoagulants
  • VKORC1 protein, human