The Prevalence of Pharmacogenomics Variants and Their Clinical Relevance Among the Pakistani Population

Abstract

Background: Pharmacogenomics (PGx), forming the basis of precision medicine, has revolutionized traditional medical practice. Currently, drug responses such as drug efficacy, drug dosage, and drug adverse reactions can be anticipated based on the genetic makeup of the patients. The pharmacogenomic data of Pakistani populations are limited. This study investigates the frequencies of pharmacogenetic variants and their clinical relevance among ethnic groups in Pakistan.

Methods: The Pharmacogenomics Knowledge Base (PharmGKB) database was used to extract pharmacogenetic variants that are involved in medical conditions with high (1A + 1B) to moderate (2A + 2B) clinical evidence. Subsequently, the allele frequencies of these variants were searched among multiethnic groups of Pakistan (Balochi, Brahui, Burusho, Hazara, Kalash, Pashtun, Punjabi, and Sindhi) using the 1000 Genomes Project (1KGP) and ALlele FREquency Database (ALFRED). Furthermore, the published Pharmacogenomics literature on the Pakistani population was reviewed in PubMed and Google Scholar.

Results: Our search retrieved (n = 29) pharmacogenetic genes and their (n = 44) variants with high to moderate evidence of clinical association. These pharmacogenetic variants correspond to drug-metabolizing enzymes (n = 22), drug-metabolizing transporters (n = 8), and PGx gene regulators, etc. (n = 14). We found 5 pharmacogenetic variants present at >50% among 8 ethnic groups of Pakistan. These pharmacogenetic variants include CYP2B6 (rs2279345, C; 70%-86%), CYP3A5 (rs776746, C; 64%-88%), FLT3 (rs1933437, T; 54%-74%), CETP (rs1532624, A; 50%-70%), and DPP6 (rs6977820, C; 61%-86%) genes that are involved in drug response for acquired immune deficiency syndrome, transplantation, cancer, heart disease, and mental health therapy, respectively.

Conclusions: This study highlights the frequency of important clinical pharmacogenetic variants (1A, 1B, 2A, and 2B) among multi-ethnic Pakistani populations. The high prevalence (>50%) of single nucleotide pharmacogenetic variants may contribute to the drug response/diseases outcome. These PGx data could be used as pharmacogenetic markers in the selection of appropriate therapeutic regimens for specific ethnic groups of Pakistan.

Keywords: Pakistan; Pharmacogenomics; allele frequency; drug-metabolizing enzymes; drug-transporters; pharmacogenetic variants.

Figure 1.

The overall design of the pharmacogenomics study.