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Combined CYP2C9, VKORC1 and CYP4F2 frequencies among racial and ethnic groups

Stuart A Scott1, Rame Khasawneh, Inga Peter

  • 1Department of Genetics & Genomic Sciences, Box 1498, Mount Sinai School of Medicine of New York University, Fifth Avenue at 100th Street, New York, NY 10029, USA.

Pharmacogenomics
|May 28, 2010
PubMed

Insights

Genetic variants in CYP2C9, VKORC1, and CYP4F2 influence warfarin dosing. African Americans have lower frequencies of the CYP4F2*3 variant, impacting genotype-guided dosing algorithms for this population.

Area of Science:

  • Pharmacogenomics
  • Genetic Epidemiology

Background:

  • Warfarin dosing is complex and influenced by genetic factors.
  • CYP4F2*3 (p.V433M) is linked to higher warfarin dose needs.
  • Systematic assessment of CYP2C9, VKORC1, and CYP4F2 variant frequencies across diverse populations is lacking.

Purpose of the Study:

  • To determine the individual and combined frequencies of key CYP2C9, VKORC1, and CYP4F2 variants.
  • To compare variant frequencies across major racial/ethnic groups, including African Americans, Asians, Caucasians, Hispanics, and Ashkenazi Jews.

Main Methods:

  • Genotyping of healthy blood donors from five distinct racial/ethnic groups.
  • Analysis included CYP2C9 (*2, *3, *4, *5, *6, *8, *11, *13), VKORC1 (g.-1639G>A), and CYP4F2 (*3 [p.V433M], rs2189784) variants.

Main Results:

  • Variant CYP2C9 allele frequencies varied significantly across groups (0.078-0.212).
  • CYP4F2*3 was prevalent in Asian, Caucasian, Hispanic, and AJ individuals (0.233-0.342) but less frequent in African Americans (0.117).
  • 87-95% of non-African American groups carried at least one variant allele (CYP2C9, VKORC1, or CYP4F2*3), compared to 53% of African Americans.

Conclusions:

  • African Americans are less likely to be homozygous for CYP4F2*3, potentially benefiting less from algorithms incorporating this variant.
  • Disparities in allele frequencies partly explain the reduced efficacy of genotype-guided warfarin dosing in African Americans.
  • Unidentified genetic or non-genetic factors may influence warfarin dosage in African Americans.
Abstract

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