Genetics
CETP variant rs1532624 is among the five most prevalent clinically relevant pharmacogenomic markers found in Pakistani ethnic groups (Evol Bioinform Online 2022)
Original title: The Prevalence of Pharmacogenomics Variants and Their Clinical Relevance Among the Pakistani Population
This study investigated the frequencies of pharmacogenetic variants with clinical relevance among eight ethnic groups of Pakistan, using the Pharmacogenomics Knowledge Base to extract variants with high to moderate clinical evidence and searching their allele frequencies via the 1000 Genomes Project and ALFRED databases. The search retrieved 29 pharmacogenetic genes and 44 variants with high to moderate clinical evidence, covering drug-metabolizing enzymes, transporters, and other regulators. Five pharmacogenetic variants were present at over 50% frequency across the ethnic groups studied: CYP2B6 rs2279345 (70%-86%), CYP3A5 rs776746 (64%-88%), FLT3 rs1933437 (54%-74%), CETP rs1532624 (50%-70%), and DPP6 rs6977820 (61%-86%), involved in drug response for AIDS, transplantation, cancer, heart disease, and mental health therapy respectively.
Original 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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.