Human N-acetyltransferase 2 ( NAT2 ) gene variability in Brazilian populations from different geographical areas.

Autor: Lopes MQP; Laboratory of Molecular Biology Applied to Mycobacteria, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, RJ, Brazil., Teixeira RLF; Laboratory of Molecular Biology Applied to Mycobacteria, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, RJ, Brazil., Cabello PH; Laboratory of Human Genetics, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, RJ, Brazil., Nery JAC; Leprosy Laboratory, Souza Araújo Outpatient Clinic, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, RJ, Brazil., Sales AM; Leprosy Laboratory, Souza Araújo Outpatient Clinic, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, RJ, Brazil., Nahn J R EP; Leprosy Outpatient Clinic, Northern Fluminense State University, Campos dos Goytacazes, RJ, Brazil., Moreira MV; Holy House of Mercy of Espírito Santo, Vitória, ES, Brazil., Stahlke EVR; Metropolitan Regional Specialty Center, Curitiba, PR, Brazil., Possuelo LG; Department of Molecular Biology and Biotechnology, IB and Biotechnology Center, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil., Rossetti MLR; Department of Molecular Biology and Biotechnology, IB and Biotechnology Center, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil., Rabahi MF; Anuar Auad Infectious Disease Reference Hospital, Goiania, GO, Brazil., Silva LFM; Municipal Secretary of Health of Palmas, Palmas, TO, Brazil., Leme PA; Municipal Secretary of Health of Gurupi, Gurupi, TO, Brazil., Woods WJ; Coordination of Sanitary Dermatology, Rio Branco, AC, Brazil., Nobre ML; Giselda Trigueiro Hospital, Natal, RN, Brazil., de Oliveira MLW; Sector of Dermatology, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil., Narahashi K; Polyclinic Oswaldo Cruz, Porto Velho, RO, Brazil., Cavalcanti M; Polyclinic Clementino Fraga, Recife, PE, Brazil., Suffys PN; Laboratory of Molecular Biology Applied to Mycobacteria, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, RJ, Brazil., Boukouvala S; Laboratory of Molecular Genetics and Pharmacogenomics - Toxicogenomics, Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupolis, Greece., Gallo MEN; Leprosy Laboratory, Souza Araújo Outpatient Clinic, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, RJ, Brazil., Santos AR; Laboratory of Molecular Biology Applied to Mycobacteria, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, RJ, Brazil.
Jazyk: angličtina
Zdroj: Frontiers in pharmacology [Front Pharmacol] 2023 Nov 15; Vol. 14, pp. 1278720. Date of Electronic Publication: 2023 Nov 15 (Print Publication: 2023).
DOI: 10.3389/fphar.2023.1278720
Abstrakt: Introduction: Several polymorphisms altering the NAT2 activity have already been identified. The geographical distribution of NAT2 variants has been extensively studied and has been demonstrated to vary significantly among different ethnic population. Here, we describe the genetic variability of human N-acetyltransferase 2 ( NAT2 ) gene and the predominant genotype-deduced acetylation profiles of Brazilians. Methods: A total of 964 individuals, from five geographical different regions, were genotyped for NAT2 by sequencing the entire coding exon. Results: Twenty-three previously described NAT2 single nucleotide polymorphisms (SNPs) were identified, including the seven most common ones globally (c.191G>A, c.282C>T, c.341T>C, c.481C>T, c.590G>A, c.803A>G and c.857G>A). The main allelic groups were NAT2*5 (36%) and NAT2*6 (18.2%), followed to the reference allele NAT2*4 (20.4%). Combined into genotypes, the most prevalent allelic groups were NAT2*5/*5 (14.6%), NAT2*5/*6 (11.9%) and NAT2*6/*6 (6.2%). The genotype deduced NAT2 slow acetylation phenotype was predominant but showed significant variability between geographical regions. The prevalence of slow acetylation phenotype was higher in the Northeast, North and Midwest (51.3%, 45.5% and 41.5%, respectively) of the country. In the Southeast, the intermediate acetylation phenotype was the most prevalent (40.3%) and, in the South, the prevalence of rapid acetylation phenotype was significantly higher (36.7%), when compared to other Brazilian states ( p < 0.0001). Comparison of the predicted acetylation profile among regions showed homogeneity among the North and Northeast but was significantly different when compared to the Southeast ( p = 0.0396). The Southern region was significantly different from all other regions ( p < 0.0001). Discussion: This study contributes not only to current knowledge of the NAT2 population genetic diversity in different geographical regions of Brazil, but also to the reconstruction of a more accurate phenotypic picture of NAT2 acetylator profiles in those regions.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2023 Lopes, Teixeira, Cabello, Nery, Sales, Nahn J. R., Moreira, Stahlke, Possuelo, Rossetti, Rabahi, Silva, Leme, Woods, Nobre, Oliveira, Narahashi, Cavalcanti, Suffys, Boukouvala, Gallo and Santos.)
Databáze: MEDLINE
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