Differences in Predicted Warfarin Dosing Requirements Between Hmong and East Asians Using Genotype-Based Dosing Algorithms

Boguang Sun; Ya-Feng Wen; Kathleen A Culhane-Pera; Muaj Lo; Txia Xiong; Koobmeej Lee; Kerui Peng; Bharat Thyagarajan; Jeffrey R Bishop; Heather Zierhut; Robert J Straka

doi:10.1002/phar.2487

Differences in Predicted Warfarin Dosing Requirements Between Hmong and East Asians Using Genotype-Based Dosing Algorithms

Pharmacotherapy. 2021 Mar;41(3):265-276. doi: 10.1002/phar.2487. Epub 2020 Dec 21.

Authors

Affiliations

¹ Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA.
² Minnesota Community Care, St. Paul, Minnesota, USA.
³ Titus Family Department of Clinical Pharmacy, School of Pharmacy, University of Southern California, Los Angeles, California, USA.
⁴ Department of Laboratory Medicine and Pathology, School of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
⁵ Department of Genetics, Cell Biology and Development, College of Biological Science, University of Minnesota, Minneapolis, Minnesota, USA.

PMID: 33202062
DOI: 10.1002/phar.2487

Abstract

Introduction: Warfarin's narrow therapeutic index and high variability in dosage requirements make dosage selection critical. Genetic factors are known to impact warfarin dosage selection. The Hmong are a unique Asian subpopulation numbering over 278,000 in the United States whose participation in genetics-based research is virtually nonexistent. The translational significance of early reports of warfarin pharmacogene differences in Hmong has not been evaluated.

Objectives: (i) To validate previously identified allele frequency differences relevant to warfarin dosing in Hmong versus East Asians and (ii) to compare predicted warfarin sensitivity and maintenance doses between a Hmong population and an East Asian cohort.

Method: DNA collected from two independent cohorts (n=236 and n=198) of Hmong adults were genotyped for CYP2C9 (*2, *3), VKORC1 (G-1639A), and CYP4F2 (*3). Allele frequencies between the combined Hmong cohort (n=433) and East Asians (n=1165) from the 2009 International Warfarin Pharmacogenetics Consortium (IWPC) study were compared using a χ² test. Percentages of Hmong and East Asian participants predicted to be very sensitive to warfarin were compared using a χ² test, and the predicted mean warfarin maintenance dose was compared with a t test.

Results: The allele frequencies of CYP2C9*3 in the combined Hmong cohort and CYP4F2*3 in the VIP-Hmong cohort are significantly different from those in East Asians (18.9% vs 3.0%, p<0.001 and 9.8% vs 22.1%, p<0.001, respectively). Comparing the combined Hmong cohort to the East Asian cohort, the percentage of participants predicted to be very sensitive to warfarin was significantly higher (28% vs 5%, p<0.01) and the mean predicted warfarin maintenance dose was significantly lower (19.8 vs 21.3 mg/week, p<0.001), respectively.

Conclusion: The unique allele frequencies related to warfarin when combined with nongenetic factors observed in the Hmong translate into clinically relevant differences in predicted maintenance dose requirements for Hmong versus East Asians.

Keywords: Asian Americans; anticoagulant drugs; minority health; pharmacogenetics; precision medicine; warfarin.

Publication types

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

MeSH terms

Adult
Algorithms
Asian People* / genetics
Genotype
Humans
Warfarin* / administration & dosage

Substances

Warfarin

Grants and funding

UL1TR002494/TR/NCATS NIH HHS/United States