The Prevalence of Pharmacogenomics Variants and Their Clinical Relevance Among the Pakistani Population
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 d...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2022-04-01
|
| Series: | Evolutionary Bioinformatics |
| Online Access: | https://doi.org/10.1177/11769343221095834 |
| _version_ | 1818476181417099264 |
|---|---|
| author | Abdul Rafay Khan Sayed Hajan Shah Sadia Ajaz Sadaf Firasat Aiysha Abid Ali Raza |
| author_facet | Abdul Rafay Khan Sayed Hajan Shah Sadia Ajaz Sadaf Firasat Aiysha Abid Ali Raza |
| author_sort | Abdul Rafay Khan |
| collection | DOAJ |
| description | 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 AL lele FRE quency D atabase (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. |
| first_indexed | 2024-12-10T09:22:07Z |
| format | Article |
| id | doaj.art-449baae271f8404dad22beda8750c302 |
| institution | Directory Open Access Journal |
| issn | 1176-9343 |
| language | English |
| last_indexed | 2024-12-10T09:22:07Z |
| publishDate | 2022-04-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Evolutionary Bioinformatics |
| spelling | doaj.art-449baae271f8404dad22beda8750c3022022-12-22T01:54:40ZengSAGE PublishingEvolutionary Bioinformatics1176-93432022-04-011810.1177/11769343221095834The Prevalence of Pharmacogenomics Variants and Their Clinical Relevance Among the Pakistani PopulationAbdul Rafay Khan0Sayed Hajan Shah1Sadia Ajaz2Sadaf Firasat3Aiysha Abid4Ali Raza5Center for Human Genetics and Molecular Medicine, Sindh Institute of Urology and Transplantation, Karachi, PakistanCenter for Human Genetics and Molecular Medicine, Sindh Institute of Urology and Transplantation, Karachi, PakistanDr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, PakistanCenter for Human Genetics and Molecular Medicine, Sindh Institute of Urology and Transplantation, Karachi, PakistanCenter for Human Genetics and Molecular Medicine, Sindh Institute of Urology and Transplantation, Karachi, PakistanCenter for Human Genetics and Molecular Medicine, Sindh Institute of Urology and Transplantation, Karachi, PakistanBackground: 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 AL lele FRE quency D atabase (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.https://doi.org/10.1177/11769343221095834 |
| spellingShingle | Abdul Rafay Khan Sayed Hajan Shah Sadia Ajaz Sadaf Firasat Aiysha Abid Ali Raza The Prevalence of Pharmacogenomics Variants and Their Clinical Relevance Among the Pakistani Population Evolutionary Bioinformatics |
| title | The Prevalence of Pharmacogenomics Variants and Their Clinical Relevance Among the Pakistani Population |
| title_full | The Prevalence of Pharmacogenomics Variants and Their Clinical Relevance Among the Pakistani Population |
| title_fullStr | The Prevalence of Pharmacogenomics Variants and Their Clinical Relevance Among the Pakistani Population |
| title_full_unstemmed | The Prevalence of Pharmacogenomics Variants and Their Clinical Relevance Among the Pakistani Population |
| title_short | The Prevalence of Pharmacogenomics Variants and Their Clinical Relevance Among the Pakistani Population |
| title_sort | prevalence of pharmacogenomics variants and their clinical relevance among the pakistani population |
| url | https://doi.org/10.1177/11769343221095834 |
| work_keys_str_mv | AT abdulrafaykhan theprevalenceofpharmacogenomicsvariantsandtheirclinicalrelevanceamongthepakistanipopulation AT sayedhajanshah theprevalenceofpharmacogenomicsvariantsandtheirclinicalrelevanceamongthepakistanipopulation AT sadiaajaz theprevalenceofpharmacogenomicsvariantsandtheirclinicalrelevanceamongthepakistanipopulation AT sadaffirasat theprevalenceofpharmacogenomicsvariantsandtheirclinicalrelevanceamongthepakistanipopulation AT aiyshaabid theprevalenceofpharmacogenomicsvariantsandtheirclinicalrelevanceamongthepakistanipopulation AT aliraza theprevalenceofpharmacogenomicsvariantsandtheirclinicalrelevanceamongthepakistanipopulation AT abdulrafaykhan prevalenceofpharmacogenomicsvariantsandtheirclinicalrelevanceamongthepakistanipopulation AT sayedhajanshah prevalenceofpharmacogenomicsvariantsandtheirclinicalrelevanceamongthepakistanipopulation AT sadiaajaz prevalenceofpharmacogenomicsvariantsandtheirclinicalrelevanceamongthepakistanipopulation AT sadaffirasat prevalenceofpharmacogenomicsvariantsandtheirclinicalrelevanceamongthepakistanipopulation AT aiyshaabid prevalenceofpharmacogenomicsvariantsandtheirclinicalrelevanceamongthepakistanipopulation AT aliraza prevalenceofpharmacogenomicsvariantsandtheirclinicalrelevanceamongthepakistanipopulation |