Sánchez Rodrigo, Acosta Oscar, Laymito Lina, Oscanoa Teodoro, Guevara-Fujita María, Moscol Saul, Obispo Daisy, Huerta Doris, Fujita Ricardo
Centro de Investigación de Genética y Biología Molecular, Facultad de Medicina Humana, Universidad de San Martín de Porres, Lima, Peru.
Facultad de Farmacia y Bioquímica, Universidad Nacional Mayor de San Marcos, Lima, Peru.
J Clin Tuberc Other Mycobact Dis. 2024 Oct 16;37:100485. doi: 10.1016/j.jctube.2024.100485. eCollection 2024 Dec.
Tuberculosis (TB) is a highly prevalent chronic infectious disease in developing countries, with Peru being one of the most affected countries in the world. The variants of the -acetyltransferase 2 () gene are related to xenobiotic metabolism and have potential usefulness in TB studies.
To determine whether gene variants and acetylator phenotypes are associated with active TB in Peruvian patients.
This study included cases (patients with TB) and controls (population-based data). First, DNA isolation and the rs1799929, rs1799930, and rs1799931 variants of the gene were identified using sequencing methods. Subsequently, the acetylator phenotypes, namely slow (SA), intermediate (IA), and rapid acetylation (RA), were also analyzed.
The comparison of the frequencies of the rs1799931 variant in the cases and controls revealed significant differences. Risk factors were found for both the A allele (p = 0.00; odds ratio [OR] = 3.04, 95 % confidence interval [CI]: 1.88-4.9) and AG genotype (p = 0.00; OR = 5.94, 95 % CI: 3.17-11.09). In addition, the non-rapid acetylator phenotype (SA + IA) was also found to be a risk factor (p = 0.016; OR = 3.16, 95 % CI: 1.29-7.72).
The A allele, GA heterozygous genotype of the rs1799931 variant of the NAT2 gene, and SA + IA acetylator phenotype showed an association with increased risk for the development of TB. In addition to xenobiotic metabolism, other metabolic and immunological functions of have also been postulated to confer susceptibility to TB in the Peruvian population owing to its characteristic high Native American component.
结核病（TB）在发展中国家是一种高度流行的慢性传染病，秘鲁是世界上受影响最严重的国家之一。N-乙酰基转移酶2（NAT2）基因的变体与异源物质代谢有关，在结核病研究中具有潜在用途。
确定NAT2基因变体和乙酰化酶表型是否与秘鲁患者的活动性结核病相关。
本研究纳入了病例（结核病患者）和对照（基于人群的数据）。首先，使用测序方法进行DNA分离并鉴定NAT2基因的rs1799929、rs1799930和rs1799931变体。随后，还分析了乙酰化酶表型，即慢乙酰化（SA）、中间乙酰化（IA）和快速乙酰化（RA）。
病例组和对照组中rs1799931变体频率的比较显示出显著差异。发现A等位基因（p = 0.00；比值比[OR] = 3.04，95%置信区间[CI]：1.88 - 4.9）和AG基因型（p = 0.00；OR = 5.94，95% CI：3.17 - 11.09）均为危险因素。此外，非快速乙酰化酶表型（SA + IA）也被发现是一个危险因素（p = 0.016；OR = 3.16，95% CI：1.29 - 7.72）。
NAT2基因rs1799931变体的A等位基因、GA杂合基因型以及SA + IA乙酰化酶表型显示与结核病发病风险增加有关。除了异源物质代谢外，由于秘鲁人群中美洲原住民成分比例高这一特征，NAT2的其他代谢和免疫功能也被推测会使该人群易患结核病。
