Generic placeholder image

Current Respiratory Medicine Reviews

Editor-in-Chief

ISSN (Print): 1573-398X
ISSN (Online): 1875-6387

Research Article

NAT2 Gene Variants as a Provocative Factor for the Severe Course of COVID-19 Pneumonia in Ukrainian Patients

Author(s): Liliia Fishchuk*, Zoia Rossokha, Valeriy Pokhylko, Yuliia Cherniavska, Svitlana Tsvirenko, Viktoriia Vershyhora, Olena Popova, Maryna Fastovets, Olena Kaliuzhka and Nataliia Gorovenko

Volume 20, Issue 1, 2024

Published on: 16 November, 2023

Page: [65 - 71] Pages: 7

DOI: 10.2174/011573398X274112231114075707

Price: $65

Abstract

Background: Previous studies indicate a close relationship between the severity of COVID-19 and oxidative stress. N-acetyltransferase 2 (NAT2) is an enzyme that metabolizes a wide range of xenobiotics and plays an important role in the regulation of reactive oxygen species, consequently contributing to the development of oxidative stress.

Aim: To determine the impact of NAT2 gene variants on the risk of developing and the progression of severe COVID-19-associated pneumonia in patients from the Poltava region of Ukraine.

Methods: The study included 117 patients who were diagnosed with severe COVID-19 pneumonia and received treatment in the intensive care unit. The NAT2 gene variants were identified through the PCR-RFLP method.

Results: The presence of the AA genotype of the A803G variant in patients with severe COVID-19 pneumonia is associated with an almost 3-fold reduction in the risk of lethal outcomes. The presence of the TT genotype of the C481T variant was associated with the need for artificial lung ventilation. Patients in the study group with a heterozygous GA genotype of the G590A variant demonstrated a notable rise in the risk of developing systemic inflammatory response syndrome and acute respiratory distress syndrome, with a nearly 2.5-fold and 3-fold increase, respectively. The G857A variant was not associated with the risk of developing the above-- mentioned complications in the examined patients.

Conclusion: The obtained results suggested that the NAT2 gene variants might influence the incidence, course, and adverse consequences of COVID-19.

Graphical Abstract

[1]
COVID-19 Dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University. Available from:https://coronavirus.jhu.edu/map.html (Accessed on: 20 July 2023).
[2]
Seligman B, Charest B, Ho YL, et al. 30-day mortality following COVID -19 and influenza hospitalization among US veterans aged 65 and older. J Am Geriatr Soc 2022; 70(9): 2542-51.
[http://dx.doi.org/10.1111/jgs.17828] [PMID: 35474510]
[3]
Nersesjan V, Amiri M, Christensen HK, Benros ME, Kondziella D. Thirty-day mortality and morbidity in COVID-19 positive vs. COVID-19 negative individuals and vs. individuals tested for Influenza A/B: A population-based study. Front Med 2020; 7: 598272.
[http://dx.doi.org/10.3389/fmed.2020.598272] [PMID: 33330562]
[4]
Kumar P, Osahon O, Vides DB, Hanania N, Minard CG, Sekhar RV. Severe glutathione deficiency, oxidative stress and oxidant damage in adults hospitalized with COVID-19: Implications for GlyNAC (Glycine and N-Acetylcysteine) supplementation. Antioxidants 2021; 11(1): 50.
[http://dx.doi.org/10.3390/antiox11010050] [PMID: 35052554]
[5]
Avila-Nava A, Pech-Aguilar AG, Lugo R, Medina-Vera I, Guevara-Cruz M, Gutiérrez-Solis AL. Oxidative stress biomarkers and their association with mortality among patients infected with SARS-CoV-2 in Mexico. Oxid Med Cell Longev 2022; 2022: 1-8.
[http://dx.doi.org/10.1155/2022/1058813] [PMID: 35746958]
[6]
Knowles JW, Xie W, Zhang Z, et al. Identification and validation of N-acetyltransferase 2 as an insulin sensitivity gene [published correction appears in J Clin Invest 2016; 126(1): 403. Chennemsetty, Indumathi [corrected to Chennamsetty, Indumathi]]. J Clin Invest 2015; 125(4): 1739-51.
[http://dx.doi.org/10.1172/JCI74692] [PMID: 25798622]
[7]
Matejcic M, Vogelsang M, Wang Y, Parker MI. Erratum to: NAT1 and NAT2 genetic polymorphisms and environmental exposure as risk factors for oesophageal squamous cell carcinoma: a case-control study. BMC Cancer 2015; 15(1): 658.
[http://dx.doi.org/10.1186/s12885-015-1681-3] [PMID: 26447020]
[8]
The single nucleotide polymorphism database (dbSNP) of nucleotide sequence variation. Available from: https://www.ncbi. nlm.nih.gov/snp/?term=NAT2 (Accessed on: 20 July 2023).
[9]
The Database of Arylamine N-Acetyltransferases (NATs). Available from:http://nat.mbg.duth.gr (Accessed on: 20 July 2023).
[10]
Procopciuc LM, Osian G, Iancu M. N-acetyl transferase 2/environmental factors and their association as a modulating risk factor for sporadic colon and rectal cancer. J Clin Lab Anal 2017; 31(5): e22098.
[http://dx.doi.org/10.1002/jcla.22098] [PMID: 27883249]
[11]
1000 Genomes Progect. Available from:http://www.ensembl.org (Accessed on: 20 July 2023).
[12]
Habil MR, Salazar-González RA, Doll MA, Hein DW. N-acetyltransferase 2 acetylator genotype-dependent N-acetylation and toxicity of the arylamine carcinogen β-naphthylamine in cryopreserved human hepatocytes. Arch Toxicol 2022; 96(12): 3257-63.
[http://dx.doi.org/10.1007/s00204-022-03381-4] [PMID: 36112171]
[13]
Habil MR, Salazar-González RA, Doll MA, Hein DW. Effect of N-acetyltransferase 2 genetic polymorphism on 4,4′-methylenebis(2-chloroaniline)-induced genotoxicity and oxidative stress. Arch Toxicol 2023; 97(6): 1773-81.
[http://dx.doi.org/10.1007/s00204-023-03508-1] [PMID: 37142755]
[14]
Liu C, Cui W, Cong L, et al. Association between NAT2 polymorphisms and lung cancer susceptibility. Medicine 2015; 94(49): e1947.
[http://dx.doi.org/10.1097/MD.0000000000001947] [PMID: 26656326]
[15]
Wu H, Wang X, Zhang L, Mo N, Lv Z. Association Between N-acetyltransferase 2 polymorphism and bladder cancer risk: results from studies of the past decade and a meta-analysis. Clin Genitourin Cancer 2016; 14(2): 122-9.
[http://dx.doi.org/10.1016/j.clgc.2015.10.007] [PMID: 26585839]
[16]
Chorfi L, Fercha A, Derouiche F, et al. N-Acetyltransferase 2, glutathione S-transferase gene polymorphisms and susceptibility to hepatocellular carcinoma in an Algerian population. Xenobiotica 2022; 52(1): 99-104.
[http://dx.doi.org/10.1080/00498254.2022.2040642] [PMID: 35138223]
[17]
Humaira I, Tahira I, Mehreen I, Ismail M, Syeda ZA, Muhammad SA. Association study of NAT2 gene polymorphism and risk of oral cancer in Southern Punjab, Pakistan. J Pak Med Assoc 2021; 71(8): 1954-8.
[http://dx.doi.org/10.47391/JPMA.1229] [PMID: 34418008]
[18]
Fayez D, Saliminejad K, Irani S, Kamali K, Memariani T, Khorram Khorshid HR. Arylamine N-acetyltransferase 2 polymorphisms and the risk of endometriosis. Avicenna J Med Biotechnol 2018; 10(3): 163-7.
[PMID: 30090210]
[19]
Trang NT, Huyen VT, Tuan NT, Phan TD. Association of N-acetyltransferase-2 and glutathione S-transferase polymorphisms with idiopathic male infertility in Vietnam male subjects. Chem Biol Interact 2018; 286: 11-6.
[http://dx.doi.org/10.1016/j.cbi.2018.03.001] [PMID: 29505746]
[20]
Zusterzeel PLM, te Morsche RHM, Raijmakers MTM, et al. N-acetyl-transferase phenotype and risk for preeclampsia. Am J Obstet Gynecol 2005; 193(3): 797-802.
[http://dx.doi.org/10.1016/j.ajog.2005.01.012] [PMID: 16150277]
[21]
Tao J, Li N, Liu Z, et al. Risk of congenital heart diseases associated with NAT2 genetic polymorphisms and maternal polycyclic aromatic hydrocarbons exposure. Prenat Diagn 2019; 39(11): 968-75.
[http://dx.doi.org/10.1002/pd.5516] [PMID: 31254350]
[22]
Padula AM, Yang W, Schultz K, et al. Genetic variation in biotransformation enzymes, air pollution exposures, and risk of spina bifida. Am J Med Genet A 2018; 176(5): 1055-90.
[http://dx.doi.org/10.1002/ajmg.a.38661] [PMID: 29681089]
[23]
Jenkins MM, Reefhuis J, Gallagher ML, et al. Maternal smoking, xenobiotic metabolizing enzyme gene variants, and gastroschisis risk. Am J Med Genet A 2014; 164(6): 1454-63.
[http://dx.doi.org/10.1002/ajmg.a.36478] [PMID: 24668907]
[24]
Wang B, Huo W, Lu Q, et al. Passive smoking and influenza-like illness in housewives: A perspective of gene susceptibility. Chemosphere 2017; 176: 67-73.
[http://dx.doi.org/10.1016/j.chemosphere.2017.02.085] [PMID: 28259080]
[25]
Hou SM, Fält S, Yang K, et al. Differential interactions between GSTM1 and NAT2 genotypes on aromatic DNA adduct level and HPRT mutant frequency in lung cancer patients and population controls. Cancer Epidemiol Biomarkers Prev 2001; 10(2): 133-40.
[PMID: 11219770]
[26]
Abbas M, Verma S, Verma S, et al. Association of GSTM1 and GSTT1 gene polymorphisms with COVID-19 susceptibility and its outcome. J Med Virol 2021; 93(9): 5446-51.
[http://dx.doi.org/10.1002/jmv.27076] [PMID: 33990973]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy