Pharmacogenomics in Asians: Differences and similarities with other human populations

ABSTRACT

Introduction

Various pharmacogenomic (PGx) variants differ widely in different ethnicities. and clinical outcomes associated with these variants may also be substantially varied. Literature was searched in different databases, i.e. PubMed, ScienceDirect, Web of Science, and PharmGKB, from inception to 30 June 2022 for this review.

Areas covered

Certain PGx variants were distinctly varied in Asian populations compared to the other human populations, e.g. CYP2C19*2,*3,*17; CYP2C9*2,*3; CYP2D6*4,*5,*10,*41; UGT1A1*6,*28; HLA-B*15:02, HLA-B*15:21, HLA-B*58:01, and HLA-A*31:01. However, certain other variants do not vary greatly between Asian and other ethnicities, e.g. CYP3A5*3; ABCB1, and SLCO1B1*5. As evident in this review, the risk of major adverse cardiovascular events (MACE) was much stronger in Asian patients taking clopidogrel and who inherited the CYP2C19 loss-of-function alleles, e.g. CYP2C19*2 and*3, when compared to the western/Caucasian patients. Additionally, the risk of carbamazepine-induced severe cutaneous adverse drug reactions (SCARs) for the patients inheriting HLA-B*15:02 and HLA-B*15:21 alleles varied significantly between Asian and other ethnicities. In contrast, both Caucasian and Asian patients inheriting the SLCO1B1*5 variant possessed a similar magnitude of muscle toxicity, i.e. myopathy.

Expert opinion

Asian countries should take measures toward expanding PGx research, as well as initiatives for the purposes of obtaining clinical benefits from this newly evolving and economically viable treatment model.

KEYWORDS:

• Pharmacogenomics
• genetic variants
• ethnicities
• safety and effectiveness
• precision medicine

Article highlights

• Different international pharmacogenomic (PGx) working groups, e.g. SEAPharm, CPIC, DPWG, U-PGx, RNPGx, and CPNDS are pioneering and advancing precision medicine for translation into clinical practice.

• Asian populations, especially East and South Asian populations, are, to a great degree, harbouring the PGx variants, which may result in substantial variations with other human populations.

• Some of the genetic variants of the metabolic enzymes, e.g. CYP2C9, CYP2C19, CYP2D6, UGT1A1, and also HLA-A/B variants differ significantly between Asian (i.e. East and South Asian) and other human populations (e.g. European, African, and American).

• Clinical outcomes (e.g. major adverse cardiovascular events (MACE)), dose-related toxicities, and severe cutaneous adverse drug reactions (SCARs) that are associated with possessing these variants may also vary significantly between Asian and other human populations.

• Asian countries should take immediate steps towards expanding PGx research and other initiatives for the purposes of accelerating clinical implementations of precision medicine.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

Mohitosh Biswas: writing—original draft preparation and visualization, review and editing; Pimonpan Jinda: writing—original draft preparation and visualization, review and editing; Chonlaphat Sukasem: Conceptualization, review and editing and supervision.

Additional information

Funding

This study was supported by the Mahidol University International Postdoctoral Fellowship, Mahidol University, Thailand.