Genetic Variation of the CYP2C9 Genetic of Minangkabau as a Predictor of Side Effect Providing Indications of Non-steroidal Anti-inflammatory Drugs
Keywords:NSAIDs, CYP2C9 gene, CYP2C9 *2/2, CYP2C9 *1/*3, Side effect
BACKGROUND: Non-steroidal Anti-inflammatory Drugs (NSAID) activity showed a varied response based on the genetic polymorphism of the CYP29C enzyme. Metabolism of some NSAIDs such as celecoxib, diclofenac, and ibuprofen is highly dependent on CYP2C9. This enzyme has several variants of the heterozygous and homozygous genotypes such as CYP2C9 *2/2 and CYP2C9 *1/*3 which differ for each population. Genetic testing for specific variations of this allele will help determine whether the drug is a valid pharmacotherapeutic option for the patient or not.
AIM: This study aims to analyze the genetic variation of the CYP2C9 gene from the Minangkabau ethnic, West Sumatra, Indonesia, which can later be used as a determinant of selecting the right NSAID with optimal effectiveness and to minimalize side effects.
MATERIAL AND METHODS: Respondents of this study were users of NSAID drugs obtained from several hospitals in Padang City and were of Minang ethnicity. Blood samples taken from patients were stored in EDTA tubes and DNA was isolated using a genomic DNA isolation kit, DNAzol® Genomic DNA Kits (Thermofischer Scientific). PCR primer and sequencing were designed using Primer Blast (NCBI) software. The synthesized primer was purified by HPLC. DNA fragment application was carried out using the PCR method. The amplicon DNA was purified and prepared as much as 500 ng for sequencing using Illumina’s Next Generation Sequencing method. This analysis was performed with the help of SPSS software.
RESULTS: When analyzing the CYP2C9 gene on Primer F23, 44 people were found to be homozygous for the normal allele (AA genotype), and 11 people were heterozygous (GT genotype), 45 people were normal allele (TT genotype), five people were heterozygous (CG genotype), 49 people were normal allele (AA genotype), and five people were heterozygous (GA genotype).CONCLUSION: This study concluded that relationship between CYP29C genetic variation and NSAID drug metabolism is found at the genotypic frequency rs229837 and rs1934969.
Plum Analytics Artifact Widget Block
Kudzi W, Dodoo AN, Mills JJ. Characterisation of CYP2C8, CYP2C9 and CYP2C19 polymorphisms in a Ghanaian population. BMC Med Genet. 2009;10(1):124. DOI: https://doi.org/10.1186/1471-2350-10-124
Burian M, Grösch S, Tegeder I, Geisslinger G. Validation of a new fluorogenic real-time PCR assay for detection of CYP2C9 allelic variants and CYP2C9 allelic distribution in a German population. Br J Clin Pharmacol. 2002;54(5):518-21. DOI: https://doi.org/10.1046/j.1365-2125.2002.01693.x
Scordo MG, Caputi AP, D’Arrigo C, Fava G, Spina E. Allele and genotype frequencies of CYP2C9, CYP2C19 and CYP2D6 in an Italian population. Pharmacol Res. 2004;50(2):195-200. https://doi.org/10.1016/j.phrs.2004.01.004 PMid:15177309 DOI: https://doi.org/10.1016/j.phrs.2004.01.004
García-Martín E, Martínez C, Ladero JM, Agúndez JA. Interethnic and intraethnic variability of CYP2C8 and CYP2C9 polymorphisms in healthy individuals. Mol Diagn Ther. 2006;10(1):29-40. https://doi.org/10.1007/BF03256440 PMid:16646575 DOI: https://doi.org/10.1007/BF03256440
Purwadi FV, Rostinawati T. Review; Pengaruh polimorfisme CYP2C9*2 dan CYP2C9*3 terahadap resiko pendarahan saluran gastroinstestinal terapi NSAID. Farmaka Suplemen. 2016;14(2):10849.
Hamblin MT, Thompson EE, Di Rienzo A. Complex signatures of natural selection at the Duffy blood group locus. Am J Hum Gen. 2002;70(2):369-83. https://doi.org/10.1086/338628 PMid:11753822 DOI: https://doi.org/10.1086/338628
Saunders MA, Hammer MF, Nachman MW. Nucleotide variability at G6pd and the signature of malarial selection in humans. Genetics. 2002;162(4):1849-61. https://doi.org/10.1093/genetics/162.4.1849 PMid:12524354 DOI: https://doi.org/10.1093/genetics/162.4.1849
Bhatti S, Aslamkhan M, Attimonelli M, Abbas S, Aydin HH. Mitochondrial DNA variation in the Sindh population of Pakistan. Aust J Forensic Sci. 2017;49(2):201-16. DOI: https://doi.org/10.1080/00450618.2016.1144788
He SM, Zhou ZW, Li XT, Zhou SF. Clinical drugs undergoing polymorphic metabolism by human cytochrome P450 2C9 and the implication in drug development. Curr Med Chem 2011;18(5):667-713. https://doi.org/10.2174/092986711794480131 PMid:21182487 DOI: https://doi.org/10.2174/092986711794480131
Ali Z, Kim RK, Ysla FM. CYP2C9 polymorphisms: Considerations in NSAID therapy. Review. Curr Opin Drug Discov Devel. 2009;12(1):108-14. PMid:19152219
Gray IC, Nobile C, Muresu R, Ford S, Spurr NK. A 2.4-megabase physical map spanning the CYP2C gene cluster on chromosome 10q24. Genomics. 1995;28(2):328-32. https://doi.org/10.1006/geno.1995.1149 PMid:8530044 DOI: https://doi.org/10.1006/geno.1995.1149
Bibi Z. Role of cytochrome P450 in drug interactions. Nutr Metabolism. 2008;5(1):1. https://doi.org/10.1186/1743-7075-5-27 PMid:18928560 DOI: https://doi.org/10.1186/1743-7075-5-27
How to Cite
Copyright (c) 2022 Yusticia Katar, Elly Usman, Gestina Aliska (Author)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.