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Potential Clinical Relevance of Differences in Allele Frequencies Found within Very Important Pharmacogenes between Hmong and East Asian Populations
Author(s) -
Wen YaFeng,
CulhanePera Kathleen A.,
Thyagarajan Bharat,
Bishop Jeffrey R.,
Zierhut Heather,
Lo Muaj,
Xiong Txia,
Peng Kerui,
Holzer Katherine,
Lee Koobmeej,
Straka Robert J.
Publication year - 2020
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/phar.2360
Subject(s) - cyp2c19 , pharmacogenetics , vkorc1 , allele frequency , allele , medicine , pharmacogenomics , genetics , slco1b1 , demography , biology , genotype , gene , sociology
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.