NAT2 gene

The NAT2 gene (NAT2 stands for N-acetyltransferase 2) is a protein-coding gene located on chromosome 8p22. Several transcript variants have been found for this gene, which code for different isoforms. An important paralog of this gene is NAT1.

This gene encodes an enzyme, N-acetyltransferase 2, which serves to both activate and deactivate arylamine and hydrazine drugs and carcinogens. Polymorphisms in this gene are responsible for the N-acetylation polymorphism, in which the human population is divided into phenotypes with fast, intermediate and slow acetylation.

Polymorphisms in this gene are also associated with higher cancer incidence and drug toxicity. A second polymorphic arylamine N-acetyltransferase gene (NAT1) is located close to this gene (NAT2). Diseases associated with NAT2 include diseases caused by acetylation disorders.

NAT2 and vitiligo: N-acetyltransferase-2 (NAT2) is a phase II enzyme that plays an important role in protecting against oxidative stress caused by reactive oxygen species. Polymorphisms in certain NAT2 genotypes can lead to an imbalance in antioxidant systems and influence the pathogenesis of vitiligo (Srivastava DSL et al. 2020). In fact, there is a significantly higher risk of vitiligo in genotypes with slow acetylators of NAT2 (Bazid HAS et al. 2024).

NAT2 and prostate cancer: Individuals with a positive smoking history/cancer history in the family together with the NAT2 slow genotype appear to have a significantly increased risk of prostate cancer (Nesa A et al. 2023). In addition, the likelihood of developing a moderate to high-grade tumor (Gleason score 7) and locally advanced or metastatic prostate cancer was significantly greater in individuals with NAT2 slow genotypes, GSTT1 and GSTM1 null genotypes.

NAT2 and psoriasis: the polymorphisms in the NAT2 gene (rs1799929, rs1799930) were each associated with an early age of onset and a severe course of the disease in one study. These polymorphisms do not represent a risk factor for the development of psoriasis. However, they can have an impact on more severe or earlier-onset cases of the disease (Dursun R et al. 2018).

NAT2 and lupus erythematosus: NAT2 genotype 857GA was more common in non-white SLE patients. The 481T allele showed a positive association with hematologic disorders involving autoimmune mechanisms, particularly autoimmune hemolytic anemia or autoimmune thrombocytopenia. LE risk may be due to environmental exposures and gene-environment interactions. Associations between SLE and occupational exposure to crystalline silica, current smoking and exogenous estrogens (e.g. oral contraceptives and postmenopausal hormones) are suspected (Woo JMP et al. 2022).

1. Bazid HAS et al. (2024) N-acetyltransferase 2 gene polymorphism and its serum levels in vitiligo patients. J Immunoassay Immunochem 45: 518-528.
2. Brooks CC et al. (2021) NAT1 genetic variation increases asthma risk in children with secondhand smoke exposure. J Asthma 58:284-292.
3. Dursun R et al. (2018) NAT2 Gene Polymorphisms in Turkish Patients with Psoriasis Vulgaris. Biomed Res Int 2018:3258708.
4. Ouerhani S et al. (2009) Combined effect of NAT2, MTR and MTHFR genotypes and tobacco on bladder cancer susceptibility in Tunisian population. Cancer Detect Prev 32:395-402.
5. Makarova SI et al. (2005) Polymorphism of arylamine-N-acetyltransferase 2 gene is associated with the risk of atopic dermatitis. Bull Exp Biol Med 139:662-664.
6. Ma XF et al. (2017) Efficacy research of salazosulfamide in ankylosing spondylitis and NAT1 gene polymorphism. Exp Ther Med 14:2999-3003.
7. Nesa A et al. (2023) Association of NAT2, GSTT1, and GSTM1 gene polymorphisms withprostate cancer risk in Bangladeshi population. Genes 868:147368.
8. Santos EC et al. (2016) Polymorphisms in NAT2 (N-acetyltransferase 2) gene in patients with systemic lupus erythematosus. Rev Bras Reumatol Engl Ed 56: 521-529.
9. Srivastava DSL et al (2020) Is NAT2 Gene Polymorphism Associated with Vitiligo? Indian J Dermatol 65:173-177.
10. Thier R et al. (2003) Markers of genetic susceptibility in human environmental hygiene and toxicology: the role of selected CYP, NAT and GST genes. Int J Hyg Environ Health 206:149-171
11. Woo JMP et al. (2022) The role of environmental exposures and gene-environment interactions in the etiology of systemic lupus erythematous. J Intern Med 291:755-778