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TNF -308G>A Single Nucleotide Polymorphism Is Associated With Leprosy Among Brazilians: A Genetic Epidemiology Assessment, Meta-Analysis, and Functional Study

2011; Oxford University Press; Volume: 204; Issue: 8 Linguagem: Inglês

10.1093/infdis/jir521

1537-6613

Cynthia Chester Cardoso, Ana Carla Pereira, Vânia Niéto Brito de Souza, Sandra Maria Barbosa Durães, Marcelo Ribeiro‐Alves, José A. C. Nery, Angela Schneider Francio, Patrícia Rosa Vanderborght, Francisco Paulo Contador Parelli, Andrea Alter, Jorge L. Salgado, Elizabeth P. Sampaio, Adalberto Rezende Santos, Maria Leide WR Oliveira, Euzenir Nunes Sarno, Erwin Schurr, Marcelo Távora Mira, Antônio Guilherme Pacheco, Milton Ozório Moraes,

Infectious Diseases and Tuberculosis

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.