RESUMO
Several genetic cytokine gene variants have been associated with host susceptibility to infectious diseases, including tuberculosis. Based upon the importance of IFN-gamma in protective immunity against Mycobacterium tuberculosis, and the functional role of the IFN-gamma + 874T/A single nucleotide polymorphism in IFN-gamma production, we genotyped 93 Brazilian tuberculosis patients and 266 asymptomatic health care workers, including 150 individuals with a positive tuberculin skin test, and analyzed the possible association of the +874A low IFN-gamma producer allele with tuberculosis occurrence. Using multivariable logistic regression models, genotype and allele frequencies of the mutant + 874A (low IFN-gamma producer) allele were significantly associated with tuberculosis disease. Heterozygous carriers had a 25% increased chance, while individuals presenting the A/A homozygous genotype had an over two-fold risk of having active tuberculosis (95% CI, 1.16-5.91, P = 0.03). Despite the mixed ethnicity observed in Brazilian populations, the present data agree with observations reported in other populations and thus demonstrate that the functional +874T/A IFN-gamma gene polymorphism is associated with tuberculosis in different populations.
Assuntos
Interferon gama/genética , Polimorfismo de Nucleotídeo Único , Tuberculose/genética , Brasil/epidemiologia , Frequência do Gene , Predisposição Genética para Doença/genética , Genótipo , Humanos , Interferon gama/metabolismo , Modelos Logísticos , Tuberculose/imunologiaRESUMO
Arylamine N-acetyltranferase 2 is the main enzyme responsible for the isoniazid metabolization into hepatotoxic intermediates and the degree of hepatotoxicity severity has been attributed to genetic variability in the NAT2 gene. The main goal of this study was to describe the genetic profile of the NAT2 gene in individuals from two different regions of Brazil: Rio de Janeiro and Goiás States. Therefore, after preparation of DNA samples from 404 individuals, genotyping of the coding region of NAT2 was performed by direct PCR sequencing. Thirteen previously described SNPs were detected in these Brazilian populations, from which seven: 191 G>A; 282 C>T; 341 T>C; 481 C>T; 590 G>A; 803 A>G and 857 G>A are the most frequent in other populations. The presence of so-called ethnic-specific SNPs in our population is in accordance with the Brazilians' multiple ancestry. Upon allele and genotype analysis, the most frequent NAT2 alleles were respectively NAT2*5B (33%), NAT2*6A (26%) and NAT2*4 (20%) being NAT2*5/*5 the more prevalent genotype (31.7%). These results clearly demonstrate the predominance in the studied Brazilian groups of NAT2 alleles associated with slow over the fast and intermediate acetylator genotypes. Additionally, in Rio de Janeiro, a significantly higher frequency of intermediate acetylation status was found when compared to Goiás (42.5% versus 25%) (p=0.05), demonstrating that different regions of a country with a population characterized by a multi-ethnic ancestry may present a large degree of variability in NAT2 allelic frequencies. This finding has implications in the determination of nationwide policies for use of appropriate anti-TB drugs.
Assuntos
Arilamina N-Acetiltransferase/genética , Polimorfismo de Nucleotídeo Único , Alelos , Antituberculosos/efeitos adversos , Antituberculosos/metabolismo , Arilamina N-Acetiltransferase/metabolismo , Sequência de Bases , Brasil , Primers do DNA/genética , Etnicidade/genética , Frequência do Gene , Genética Populacional , Genótipo , Humanos , Isoniazida/efeitos adversos , Isoniazida/metabolismo , FarmacogenéticaRESUMO
Introdução: a amplificação de ácido nucleico através da técnica de reaçã em cadeia da polimerase - PCR pode ser útil para o diagnóstico da tuberculose. O objetivo deste trabalho foi padronizar um método molecular para o diagnóstico da TB pulmonar. Material e métodos: iniciadores especificos foram usados para amplificação...
