CYP2C9*61, a rare missense variant identified in a Puerto Rican patient with low warfarin dose requirements

Pharmacogenomics. 2019 Jan;20(1):3-8. doi: 10.2217/pgs-2018-0143. Epub 2018 Dec 6.

Abstract

Warfarin continues to be the mainstay therapy for preventing thrombus formation. Although pharmacogenetic algorithms have shown higher predictability of the optimal warfarin dose and lower occurrence of bleeding episodes, they often do not include ethno-specific genetic variants relevant to non-Europeans. This case report describes a rare missense variant at exon 9 of CYP2C9 (rs202201137; c.1370A>G transition; p.Asn457Ser) found in a Puerto Rican patient with low warfarin dose requirements (3 mg/day). The haplotype characterized by two amino acid changes, Asn457Ser and Arg144Cys (rs1799853; c.430C>T), has been designated CYP2C9*61 by the Pharmacogene Variation Consortium. According to prediction scores assessed with the Combined Annotation Dependent Depletion tool, CYP2C9*61 (p.Asn457Ser) was classified as nondeleterious, therefore its impact on CYP2C9 enzymatic activity cannot be postulated.

Keywords: Hispanics; anticoagulation; haplotype; next-generation sequencing; pharmacogenetics (PGx); warfarin.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anticoagulants / administration & dosage*
  • Cytochrome P-450 CYP2C9 / genetics*
  • Genotype
  • Hispanic or Latino / genetics*
  • Humans
  • Male
  • Mutation, Missense / genetics*
  • Pharmacogenetics / methods
  • Warfarin / administration & dosage*

Substances

  • Anticoagulants
  • Warfarin
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9