Potential Clinical Relevance of Differences in Allele Frequencies Found within Very Important Pharmacogenes between Hmong and East Asian Populations

Ya Feng Wen, Kathleen A. Culhane-Pera, Bharat Thyagarajan, Jeffrey R. Bishop, Heather Zierhut, Muaj Lo, Txia Xiong, Kerui Peng, Katherine Holzer, Koobmeej Lee, Robert J. Straka

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Objectives: Implementing pharmacogenetics for very important pharmacogenes (VIPs) holds the promise of improving clinical outcomes through optimal medication selection and dosing. However, significant differences in the frequency of actionable variants in VIPs may exist within subpopulations of a given ancestral group. Furthermore, these differences can potentially impact drug selection and dosing. The purpose of this study was to ascertain allele frequencies for VIPs and to predict medication requirements using Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines in Hmong and compare with published data for East Asians. Methods: Using a community-based participatory action research approach, DNA collected from 194 Hmong adults living in the United States was analyzed for 22 genetic variants within eight VIPs (CYP2C9, CYP2C19, CYP4F2, DPYD, G6PD, SLCO1B1, TPMT, VKORC1). Allele frequencies for VIPs and predicted medication requirements using CPIC guidelines were compared between Hmong participants and East Asians. Results: Significant differences in allele frequencies between the Hmong and East Asians were found for 23% (5/22) of the CPIC-actionable variants tested. Allele frequencies for VIPs in Hmong versus East Asians were 16.6% versus 3.4% in CYP2C9*3A, 42.2% versus 29.0% for CYP2C19*2, 0.3% versus 8.3% in CYP2C19*3, 6.5% versus 22.1% in CYP4F2*3, and 3.6% versus 0.1% in SLCO1B1*5, respectively. These differences significantly influenced predicted medication usage recommendations in warfarin, simvastatin, and phenytoin between Hmong and East Asians. Conclusions: Important differences in allele frequencies for key genetic variants influencing selection of medications and dosages were found between the Hmong and East Asians. The magnitude and nature of these differences can be expected to result in different medication recommendations for the Hmong relative to East Asians.

Original languageEnglish (US)
Pages (from-to)142-152
Number of pages11
JournalPharmacotherapy
Volume40
Issue number2
DOIs
StatePublished - Feb 1 2020

Bibliographical note

Funding Information:
The authors wish to thank the support from all the participants and the Hmong Genomic Community. In addition, we appreciate Dr. Helene Barcelo‐Larson and staff in University of Minnesota Molecular Diagnostics Laboratory and Genomic Center for their invaluable assistance. This study was supported by the Grand Challenge Exploratory Research Award, Office of the Executive Vice President and Provost, University of Minnesota and National Institutes of Health's National Center for Advancing Translational Sciences, grant UL1TR002494. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health's National Center for Advancing Translational Sciences.

Keywords

  • Asian Americans
  • Hmong
  • gene frequency
  • minority health
  • pharmacogenetics
  • precision medicine

PubMed: MeSH publication types

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

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