Substantiation of a clopidogrel metabolism-associated gene (CYP2C19) variation among healthy individuals
Background: It is essential to investigate the prevalence of CYP2C19 alleles that affect drug metabolism. This study measures the allelic and genotypic frequencies of CYP2C19 loss-of-function (LoF) alleles CYP2C19∗2, CYP2C19∗3, and gain-of-function (GoF) alleles CYP2C19∗17 in the general population....
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | Indian Heart Journal |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0019483223000883 |
| _version_ | 1797666825421455360 |
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| author | Anshu Kumar Yadav Aparna Kodakkat Chakkumkollath Aysha Helna Siddharth Birla Rajesh Kumar Thimmulappa Sunil Kumar Shambu Prashant Vishwanath Akila Prashant |
| author_facet | Anshu Kumar Yadav Aparna Kodakkat Chakkumkollath Aysha Helna Siddharth Birla Rajesh Kumar Thimmulappa Sunil Kumar Shambu Prashant Vishwanath Akila Prashant |
| author_sort | Anshu Kumar Yadav |
| collection | DOAJ |
| description | Background: It is essential to investigate the prevalence of CYP2C19 alleles that affect drug metabolism. This study measures the allelic and genotypic frequencies of CYP2C19 loss-of-function (LoF) alleles CYP2C19∗2, CYP2C19∗3, and gain-of-function (GoF) alleles CYP2C19∗17 in the general population. Methodology: The study involved 300 healthy subjects between the ages of 18 and 85 recruited by simple random sampling. Allele-specific touchdown PCR was employed to identify the various alleles. The genotype and allele frequencies were calculated and checked for Hardy–Weinberg equilibrium. The phenotypic prediction of ultra-rapid metabolizer (UM = ∗17/∗17), extensive metabolizer (EM = ∗1/∗17, ∗1/∗1), intermediate metabolizer (IM = ∗1/∗2, ∗1/∗3, ∗2/∗17) and poor metabolizer (PM = ∗2/∗2, ∗2/∗3, ∗3/∗3) was made based on their genotype. Results: The allele frequency of CYP2C19∗2, CYP2C19∗3, and CYP2C19∗17 was 0.365, 0.0033, and 0.18, respectively. The IM phenotype predominated with an overall frequency of 46.67%, including 101 subjects with ∗1/∗2, two subjects with ∗1/∗3, and 37 subjects with ∗2/∗17 genotype. This was followed by EM phenotype with an overall frequency of 35%, including 35 subjects with ∗1/∗17 and 70 subjects with ∗1/∗1 genotype. PM phenotype had an overall frequency of 12.67%, including 38 subjects with ∗2/∗2 genotype, and UM phenotype had an overall frequency of 5.67%, including 17 subjects with ∗17/∗17 genotype. Conclusion: Given the high allelic frequency of PM in the study population, a pre-treatment test to identify the individual's genotype may be recommended to decide the dosage, monitor the drug response, and avoid adverse drug reactions. |
| first_indexed | 2024-03-11T20:05:06Z |
| format | Article |
| id | doaj.art-1af99059f6e245d2a7133f453e422824 |
| institution | Directory Open Access Journal |
| issn | 0019-4832 |
| language | English |
| last_indexed | 2024-03-11T20:05:06Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Indian Heart Journal |
| spelling | doaj.art-1af99059f6e245d2a7133f453e4228242023-10-04T04:13:54ZengElsevierIndian Heart Journal0019-48322023-09-01755343346Substantiation of a clopidogrel metabolism-associated gene (CYP2C19) variation among healthy individualsAnshu Kumar Yadav0Aparna Kodakkat Chakkumkollath1Aysha Helna2Siddharth Birla3Rajesh Kumar Thimmulappa4Sunil Kumar Shambu5Prashant Vishwanath6Akila Prashant7Center of Excellence in Molecular Biology and Regenerative Medicine, Department of Biochemistry, JSS Medical College, JSS Academy of Higher Education & Research, Mysuru, IndiaCenter of Excellence in Molecular Biology and Regenerative Medicine, Department of Biochemistry, JSS Medical College, JSS Academy of Higher Education & Research, Mysuru, IndiaCenter of Excellence in Molecular Biology and Regenerative Medicine, Department of Biochemistry, JSS Medical College, JSS Academy of Higher Education & Research, Mysuru, IndiaCenter of Excellence in Molecular Biology and Regenerative Medicine, Department of Biochemistry, JSS Medical College, JSS Academy of Higher Education & Research, Mysuru, IndiaCenter of Excellence in Molecular Biology and Regenerative Medicine, Department of Biochemistry, JSS Medical College, JSS Academy of Higher Education & Research, Mysuru, IndiaDepartment of Cardiology, JSS Medical College, JSS Academy of Higher Education & Research, Mysuru, IndiaCenter of Excellence in Molecular Biology and Regenerative Medicine, Department of Biochemistry, JSS Medical College, JSS Academy of Higher Education & Research, Mysuru, IndiaCenter of Excellence in Molecular Biology and Regenerative Medicine, Department of Biochemistry, JSS Medical College, JSS Academy of Higher Education & Research, Mysuru, India; Special Interest Group – Human Genomics and Rare Disorders, JSS Academy of Higher Education & Research, Mysuru, India; Corresponding author. Center of Excellence in Molecular Biology and Regenerative Medicine, Department of Biochemistry, JSS Medical College, JSS Academy of Higher Education & Research, Mysuru, India.Background: It is essential to investigate the prevalence of CYP2C19 alleles that affect drug metabolism. This study measures the allelic and genotypic frequencies of CYP2C19 loss-of-function (LoF) alleles CYP2C19∗2, CYP2C19∗3, and gain-of-function (GoF) alleles CYP2C19∗17 in the general population. Methodology: The study involved 300 healthy subjects between the ages of 18 and 85 recruited by simple random sampling. Allele-specific touchdown PCR was employed to identify the various alleles. The genotype and allele frequencies were calculated and checked for Hardy–Weinberg equilibrium. The phenotypic prediction of ultra-rapid metabolizer (UM = ∗17/∗17), extensive metabolizer (EM = ∗1/∗17, ∗1/∗1), intermediate metabolizer (IM = ∗1/∗2, ∗1/∗3, ∗2/∗17) and poor metabolizer (PM = ∗2/∗2, ∗2/∗3, ∗3/∗3) was made based on their genotype. Results: The allele frequency of CYP2C19∗2, CYP2C19∗3, and CYP2C19∗17 was 0.365, 0.0033, and 0.18, respectively. The IM phenotype predominated with an overall frequency of 46.67%, including 101 subjects with ∗1/∗2, two subjects with ∗1/∗3, and 37 subjects with ∗2/∗17 genotype. This was followed by EM phenotype with an overall frequency of 35%, including 35 subjects with ∗1/∗17 and 70 subjects with ∗1/∗1 genotype. PM phenotype had an overall frequency of 12.67%, including 38 subjects with ∗2/∗2 genotype, and UM phenotype had an overall frequency of 5.67%, including 17 subjects with ∗17/∗17 genotype. Conclusion: Given the high allelic frequency of PM in the study population, a pre-treatment test to identify the individual's genotype may be recommended to decide the dosage, monitor the drug response, and avoid adverse drug reactions.http://www.sciencedirect.com/science/article/pii/S0019483223000883CYP2C19HumanAdverse drug eventsPharmacogenomicsClopidogrel |
| spellingShingle | Anshu Kumar Yadav Aparna Kodakkat Chakkumkollath Aysha Helna Siddharth Birla Rajesh Kumar Thimmulappa Sunil Kumar Shambu Prashant Vishwanath Akila Prashant Substantiation of a clopidogrel metabolism-associated gene (CYP2C19) variation among healthy individuals Indian Heart Journal CYP2C19 Human Adverse drug events Pharmacogenomics Clopidogrel |
| title | Substantiation of a clopidogrel metabolism-associated gene (CYP2C19) variation among healthy individuals |
| title_full | Substantiation of a clopidogrel metabolism-associated gene (CYP2C19) variation among healthy individuals |
| title_fullStr | Substantiation of a clopidogrel metabolism-associated gene (CYP2C19) variation among healthy individuals |
| title_full_unstemmed | Substantiation of a clopidogrel metabolism-associated gene (CYP2C19) variation among healthy individuals |
| title_short | Substantiation of a clopidogrel metabolism-associated gene (CYP2C19) variation among healthy individuals |
| title_sort | substantiation of a clopidogrel metabolism associated gene cyp2c19 variation among healthy individuals |
| topic | CYP2C19 Human Adverse drug events Pharmacogenomics Clopidogrel |
| url | http://www.sciencedirect.com/science/article/pii/S0019483223000883 |
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