Laboratório de Hanseníase, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Brazil.
J Infect Dis. 2011 Oct 15;204(8):1256-63. doi: 10.1093/infdis/jir521.
Leprosy is an infectious disease caused by Mycobacterium leprae. Tumor necrosis factor (TNF) plays a key role in the host response. Some association studies have implicated the single nucleotide polymorphism TNF -308G>A in leprosy susceptibility, but these results are still controversial. We first conducted 4 association studies (2639 individuals) that showed a protective effect of the -308A allele (odds ratio [OR] = 0.77; P = .005). Next, results of a meta-analysis reinforced this association after inclusion of our new data (OR = 0.74; P = .04). Furthermore, a subgroup analysis including only Brazilian studies suggested that the association is specific to this population (OR = 0.63; P = .005). Finally, functional analyses using whole blood cultures showed that patients carrying the -308A allele produced higher TNF levels after lipopolysaccharide (LPS) (6 hours) and M. leprae (3 hours) stimulation. These results reinforce the association between TNF and leprosy and suggest the -308A allele as a marker of disease resistance, especially among Brazilians.
麻风病是由麻风分枝杆菌引起的传染病。肿瘤坏死因子（TNF）在宿主反应中起着关键作用。一些关联研究表明 TNF-308G>A 单核苷酸多态性与麻风病易感性有关，但这些结果仍存在争议。我们首先进行了 4 项关联研究（2639 人），表明 -308A 等位基因具有保护作用（比值比 [OR] = 0.77；P =.005）。接下来，包含我们新数据的荟萃分析结果强化了这种关联（OR = 0.74；P =.04）。此外，仅包括巴西研究的亚组分析表明，这种关联是特定于该人群的（OR = 0.63；P =.005）。最后，使用全血培养进行的功能分析表明，携带 -308A 等位基因的患者在脂多糖（LPS）（6 小时）和麻风分枝杆菌（3 小时）刺激后产生更高水平的 TNF。这些结果加强了 TNF 与麻风病之间的关联，并表明 -308A 等位基因是疾病抵抗力的标志物，尤其是在巴西人中。
