Pharmacogenomics in Asian subpopulations and impacts on commonly prescribed medications.

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Abstract

Asians as a group comprise of over 60% the world's population. There is an incredible amount of diversity in Asian and admixed populations that has not been studied in a pharmacogenetic context. The known pharmacogenetic differences in Asians subgroups generally represent previously known variants that are present at much lower or higher frequencies in Asians compared to other populations. This review aims to 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 Food and Drug Administration (FDA) and the Clinical Pharmacogenetics Implementation Consortium (CPIC) 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 CYP2C19 poor metabolizers and carriers of the HLA-B*15:02 allele. The relative risk increase seen ranged between genes and drugs but could be over 100x more likely in Asians such as the 172x increase in risk of SJS and TEN with carbamazepine use amongst 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 dosing and medication choice for at risk populations. Further studies should be done on Asian cohorts to more fully understand pharmacogenetic variants in these populations to understand how such differences may influence drug response.

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