Pharmacogenomics in Asian Subpopulations and Impacts on Commonly Prescribed Medications

Abstract

Asians as a group comprise > 60% the world’s population. There is an incredible amount of diversity in Asian and admixed populations that has not been addressed in a pharmacogenetic context. The known pharmacogenetic differences in Asian subgroups generally represent previously known variants that are present at much lower or higher frequencies in Asians compared with other populations. In this review we summarize the main drugs and known genes that appear to have differences in their pharmacogenetic properties in certain Asian populations. Evidence‐based guidelines and summary statistics from the US Food and Drug Administration and the Clinical Pharmacogenetics Implementation Consortium were analyzed for ethnic differences in outcomes. Implicated drugs included commonly prescribed drugs such as warfarin, clopidogrel, carbamazepine, and allopurinol. The majority of these associations are due to Asians more commonly being poor metabolizers of cytochrome P450 (CYP) 2C19 and carriers of the human leukocyte antigen (HLA)‐B*15:02 allele. The relative risk increase was shown to vary between genes and drugs, but could be > 100‐fold higher in Asians. Specifically, there was a 172‐fold increased risk of Stevens‒Johnson syndrome and toxic epidermal necrolysis with carbamazepine use among HLA‐B*15:02 carriers. The effects ranged from relatively benign reactions such as reduced drug efficacy to severe cutaneous skin reactions. These reactions are severe and prevalent enough to warrant pharmacogenetic testing and appropriate changes in dose and medication choice for at‐risk populations. Further studies should be done on Asian cohorts to more fully understand pharmacogenetic variants in these populations and to clarify how such differences may influence drug response.

HLA‐associated adverse drug reactions ‐ scoping review

“…Accordingly, HLA‐typing and corresponding prescribing changes is warranted in Asian populations. 78 Other populations were Whites and Africans, and some studies investigated mixed populations. Interestingly, for more than 9% of the studies, ethnicity was not defined.…”

Life-time Actionable Pharmacogenetic Drug Use: A Population-based Cohort Study in 86 040 Young People With and Without Mental Disorders in Denmark

“…Lastly, the iPSYCH population is rather homogeneous with 88 % of Danish or European ancestry, 10 % mixed ancestry, and only up to 2 % of Non-European ancestry, partially due to the design of the study including individuals born in Denmark since 1981. Among the commonly used PGx drugs identified in the current study, this may affect estimates for the even greater utility of PGx testing of drugs affected by CYP2C19 variations or HLA-B variants, both of which are more frequent in individuals with Asian ancestry; or CYP2C9 variations in individuals with African ancestry and should be considered in PGx adjusted dosing recommendations of relevant drugs [46,47].…”

Applying an equity lens to pharmacogenetic research and translation to under‐represented populations

“…Systematic reviews in Africans, North American Indigenous populations, US Hispanics, Asians, Mexicans, and Brazilians share several common themes, including that there are existing differences in allele frequencies across races in common pharmacogenes, application of European‐based PGx to other races may unintentionally result in heterogeneous clinical outcomes, and that non‐European ethnicities must be represented in PGx studies both for discovery of novel variants and to guide clinical implications through population specific PGx tests and dosing algorithms. 6 , 7 , 8 , 9 , 10 , 11 …”

“…5 This review concluded that the bias of European-based genetic research translated to a non-European population can result in heterogeneous treatment outcomes. 5 Several reviews have discussed the lack of underrepresented populations in PGx studies, [6][7][8][9][10][11] all of which note an overwhelming lack of genetic diversity that will impede equitable clinical implementation through inappropriate application of gene-based dosing algorithms and by missed opportunities for identification of population-specific single nucleotide variants and alleles. Systematic reviews in Africans, North American Indigenous populations, US Hispanics, Asians, Mexicans, and Brazilians share several common themes, including that there are existing differences in allele frequencies across races in common pharmacogenes, application of European-based PGx to other races may unintentionally result in heterogeneous clinical outcomes, and that non-European ethnicities must be represented in PGx studies both for discovery of novel variants and to guide clinical implications through population specific PGx tests and dosing algorithms.…”