Preliminary identification of N-Acetyltransferase 2 (NAT2) gene polymorphisms in the dayak population
Article Sidebar
Main Article Content
Abstract
Polymorphism is a change or mutation in a gene that does not cause a change in the protein structure. The N-Acetyltransferase NAT enzyme is encoded by the N-Acetyltransferase 2 (NAT2) gene, the N-Acetyltransferase 2 (NAT2) gene, several variations of DNA known as single nucleotide polymorphisms (SNPs) that alter the genotype, haplotype, and phenotype. The NAcetyltransferase 2 (NAT2) genotype was classified into three phenotypes, namely fast acetylators, intermediate acetylators, and slow acetylators. The purpose of this study was to determine the type of polymorphism and the type of polymorphism of the NAT2 gene of the Dayak tribe. In this study, blood samples from the Dayak tribe were isolated from the Wizard Genomic DNA Purification kit and then identified Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). With stages 1. Denaturation 2. Anneling and 3. Extension using NAT2 N4 and N5 primers then RFLP with restriction enzymes KpnI, TaqI and BamHI then electrophoresed with 2% agarose gel. The results of the initial identification of the N-Acetyltransferase 2 (NAT2) gene polymorphism in the Dayak tribe obtained 5 types of genotypes NAT2*4/*5B (20%), NAT2*4/*6A (33.3%), NAT2*4/*7B (20%), NAT2*5B/5B (13.3%) and NAT2*7B/7B (13.3%). From the phenotype of the Dayak tribe, there are two medium acetylators (73.3%) and slow acetylators (26.3%).
Article Details
References
R. Yuliwulandari, R. W. Susilowati, I. Razari, K. Viyati, H. Umniyati, and K. Prayuni, “N-acetyltransferase 2 Polymorphism and Acetylation Profiles in Buginese Ethnics of Indonesia,” Ann. Hum. Genet., vol. 83, no. 6, pp. 465–471, Nov. 2019, doi: 10.1111/ahg.12341.
N. J. Butcher, S. Boukouvala, E. Sim, and R. F. Minchin, “Pharmacogenetics of the arylamine N-acetyltransferases,” Pharmacogenomics J., vol. 2, no. 1, pp. 30–42, 2002, doi: 10.1038/sj.tpj.6500053.
D. W. Hein and L. M. Millner, “Arylamine N-acetyltransferase Acetylation Polymorphisms: Paradigm for Pharmacogenomic-guided Therapy- a Focused Review,” Expert Opin. Drug Metab. Toxicol., vol. 17, no. 1, pp. 9–21, Jan. 2021, doi: 10.1080/17425255.2021.1840551.
P. Wang et al., “Deficiency of N-acetyltransferase Increases the Interactions of Isoniazid with Endobiotics in Mouse Liver,” Biochem. Pharmacol., vol. 145, pp. 218–225, Dec. 2017, doi: 10.1016/j.bcp.2017.09.001.
A. D. Wahyudi and S. Soedarsono, “Farmakogenomik Hepatotoksisitas Obat Anti Tuberkulosis,” J. Respirasi, vol. 1, no. 3, p. 103, 2019, doi: 10.20473/jr.v1-i.3.2015.103-108.
K. Zhu et al., “Association Between NAT2 Polymorphism and Lung Cancer Risk: A Systematic Review and Meta-Analysis,” Front. Oncol., vol. 11, no. March, pp. 1–9, 2021, doi: 10.3389/fonc.2021.567762.
R. Yuliwulandari, K. Prayuni, H. Usman, Q. Sachrowardi, and K. Tokunaga, “Differentiation of n-acetyltransferase 2 (NAT2) Rapid and Intermediate Acetylator Based on Genotype and Urinary Assay,” Australas. Med. J., vol. 10, no. 10, pp. 879–883, 2017, doi: 10.21767/AMJ.2017.3105.
R. W. Susilowati, K. Prayuni, I. Razari, S. Bahri, and R. Yuliwulandari, “High frequency of NAT2 slow acetylator alleles in the Malay population of Indonesia: An awareness to the anti-tuberculosis drug induced liver injury and cancer,” Med. J. Indones., vol. 26, no. 1, pp. 7–13, 2017, doi: 10.13181/mji.v26i1.1563.
A. Dilhari et al., “Evaluation of the Impact of Six Different DNA Extraction Methods for the Representation of the Microbial Community Associated with Human Chronic Wound Infections Using a Gel-based DNA Profiling Method,” AMB Express, vol. 7, no. 1, p. 179, Sep. 2017, doi: 10.1186/s13568-017-0477-z.
G. Lucena-Aguilar, A. M. Sánchez-López, C. Barberán-Aceituno, J. A. Carrillo-Ávila, J. A. López-Guerrero, and R. Aguilar-Quesada, “DNA Source Selection for Downstream Applications Based on DNA Quality Indicators Analysis,” Biopreserv. Biobank., vol. 14, no. 4, pp. 264–270, Aug. 2016, doi: 10.1089/bio.2015.0064.
D. Yadav et al., “Association of Nat2 Gene Polymorphism with Association of Nat2 Gene Polymorphism with Antitubercular Drug-induced Hepatotoxicity in the Eastern Uttar Pradesh Population,” Cureus, vol. 11, no. 4, pp. 2–9, 2019, doi: 10.7759/cureus.4425.
A. D. Malewa, “Diversity of the Palu Sheep Growth Hormone Gene using the PCR-RFLP Method,” 2019, [Online]. Available: https://api.semanticscholar.org/CorpusID:226793995.
P. M. Skowron et al., “The Third Restriction-modification System from Thermus aquaticus YT-1: Solving the Riddle of Two TaqII Specificities,” Nucleic Acids Res., vol. 45, no. 15, pp. 9005–9018, Sep. 2017, doi: 10.1093/nar/gkx599.
X. Lv et al., “NAT2 Genetic Polymorphisms and Anti-tuberculosis Drug-Induced Hepatotoxicity in Chinese Community Population,” Ann. Hepatol., vol. 11, no. 5, pp. 700–707, 2012, doi: https://doi.org/10.1016/S1665-2681(19)31446-2.
S. K. Sharma et al., “Genetic Polymorphisms of N-acetyltransferase 2 & Susceptibility to Antituberculosis Drug-induced Hepatotoxicity,” Indian J. Med. Res., vol. 144, no. 6, pp. 924–928, Dec. 2016, doi: 10.4103/ijmr.IJMR_684_14.
R. Yuliwulandari et al., “Polymorphisms of promoter and coding regions of the arylamine N-acetyltransferase 2 (NAT2) gene in the Indonesian population: proposal for a new nomenclature.,” J. Hum. Genet., vol. 53, no. 3, pp. 201–209, 2008, doi: 10.1007/s10038-007-0237-z.
R. A. Salazar-González, E. Turiján-Espinoza, D. W. Hein, R. C. Milán-Segovia, E. E. Uresti-Rivera, and D. P. Portales-Pérez, “Expression and Genotype-dependent Catalytic Activity of N-acetyltransferase 2 (NAT2) in Human Peripheral Blood Mononuclear Cells and Its Modulation by Sirtuin 1,” Biochem. Pharmacol., vol. 156, pp. 340–347, Oct. 2018, doi: 10.1016/j.bcp.2018.08.034.
K. Fukino et al., “Effects of N-acetyltransferase 2 (NAT2), CYP2E1 and Glutathione-S-transferase (GST) Genotypes on the Serum Concentrations of Isoniazid and Metabolites in Tuberculosis Patients.,” J. Toxicol. Sci., vol. 33, no. 2, pp. 187–195, May 2008, doi: 10.2131/jts.33.187.
L. V. I. Dewi, “Hubungan Variasi Genetika NAT2 terhadap Risiko Adverse Drug Reaction ( ADR ) dan Outcome Klinis Pasien Tuberkulosis Suku Jawa,” Universitas Gadjah Mada, 2020.
V. Kukongviriyapan, A. Prawan, W. Tassaneyakul, J. Aiemsa-Ard, and B. Warasiha, “Arylamine N-acetyltransferase-2 Genotypes in the Thai Population.,” Br. J. Clin. Pharmacol., vol. 55, no. 3, pp. 278–281, Mar. 2003, doi: 10.1046/j.1365-2125.2003.01766.x.
V. Yunivita et al., “Isoniazid Exposures and Acetylator Status in Indonesian Tuberculous Meningitis Patients,” Tuberculosis (Edinb)., vol. 144, p. 102465, Jan. 2024, doi: 10.1016/j.tube.2023.102465.
A. Mukherjee, T. Velpandian, M. Singla, K. Kanhiya, S. K. Kabra, and R. Lodha, “Pharmacokinetics of Isoniazid, Rifampicin, Pyrazinamide and Ethambutol in Indian Children,” BMC Infect. Dis., vol. 15, no. 1, p. 126, 2015, doi: 10.1186/s12879-015-0862-7.
S. Soedarsono et al., “Development of Population Pharmacokinetics Model of Isoniazid in Indonesian Patients with Tuberculosis,” Int. J. Infect. Dis., vol. 117, pp. 8–14, Apr. 2022, doi: 10.1016/j.ijid.2022.01.003.
R. Mahajan and A. K. Tyagi, “Pharmacogenomic Insights Into Tuberculosis Treatment Shows the NAT2 Genetic Variants Linked to Hepatotoxicity Risk: a Systematic Review and Meta-Analysis,” BMC Genomic Data, vol. 25, no. 1, p. 103, 2024, doi: 10.1186/s12863-024-01286-y.
R. Yuliwulandari et al., “NAT2 Variants are Associated with Drug-induced Liver Injury Caused by Anti-tuberculosis Drugs in Indonesian Patients with Tuberculosis.,” J. Hum. Genet., vol. 61, no. 6, pp. 533–537, Jun. 2016, doi: 10.1038/jhg.2016.10.