Ethnicity-inclusive PGx testing

Ethnicity-inclusive PGx testing

Why ethnicity inclusive PGx testing?

For racial and ethnic minorities in the United States, health disparities take on many forms. Causes of health disparities are multifaceted1. Genetic variations contribute to the interindividual variability in drug responses and may explain part of the healthcare disparity among diverse populations2.

At RPRD, we believe in order to provide the best quality PGx test results to every patient, a test needs to investigate not only the common alleles, as most of the commercial PGx tests focus on, but also these rare alleles, especially the ethnicity-specific variants.

Allele frequencies differ among populations.

The allele frequency represents the incidence of a gene variant in a population. Many of alleles affecting major drug metabolism pathways show striking population difference in allele frequency. Figure 1 illustrates the allele frequencies of a few frequently test PGx genes. For example, ethnicity specific CYP2C9 *8 and *11 alleles have been shown to improve warfarin dose prediction in African American3. An African American patient could be misclassified if  *8 and *11 are not integrated in the test.


Figure 1. Examples of allele frequencies of CYP2C9, CYP2C19 and CYP2D6 in some ethnicity groups4

Warfarin PGx example: the importance of testing ethnicity-specific alleles

VKORC1 -1639 G>A SNP provides greater contribution to the variability in dose among European than non-European, largely explained by the allele frequency5.

CYP2C9 *5, *6, *8 and *11 are identified in African, but essentially absent in non-African populations6.

A GWAS study revealed a novel association between rs12777823 and warfarin clearance in African American, but not in European or Asian7. 40% of the African American has the variant, suggesting failure to account for the variant could lead to over-dose for a significant portion of the African American population.

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An African American male was enrolled into the PG4KDS PGx clinical trial at St. Jude Children’s Research Hospital. Previous genotyping by a competitor’s CYP2D6 assay reported a *4/*17 diplotype (intermediate metabolizer). However, this CYP2D6 assay was not designed to detect the *40 allele. Subsequent genotyping by RPRD detected CYP2D6 *4/*40 genotype (poor metabolizer). RPRD’s comprehensive approach yields ethnicity-unbiased testing result, which is essential for analyzing diverse populations.

  • CYP2D6 *40 is most commonly observed in the African population and differs from *17 by the presence of an in-frame insertion variant rs72549356. There is significant clinical relevance of the variant: *17 has reduced function, while *40 has no function. Most commercial CYP2D6 genotyping tests do not include this variant, and thus would have assigned an inaccurate phenotype.

My team and I are very proud of the tests we offer because they are developed using strong peer-reviewed scientific evidence and the industry’s highest standards. Our goal is to ensure that patients receive the most up-to-date, comprehensive and accurate results possible.

PGx Testimonial

- Amy Turner, Director of Operations and Innovation

Genes and alleles

Learn more about the genes and alleles included in the WPS testing

Genes and drugs

Learn more about the genes and drugs included in the WPS testing

  1. Communities in Action: Pathway to Health Equity. National Academies of Sciences, Engineering and Medicine, 2017
  2. Zhang, et al. clinical Pharmacology & Therapeutics. 106 (2); 338
  3. Hernandez et al. Pharmaconom. J. 2014. 14, 223
  5. CPIC guideline for PGx-guided warfarin dosing. Clin Pharmacol Ther. 2017. 102 (3). 397
  6. Perera, et al. Clin Pharmacol Ther. 2014. 95 (3): 242
  7. Pera et al. Lancet. 2013. 382: 790
  8. Hoshtsuki, K. et al. Genetics in Medicine. 2020. 22 (1): 232