1. TNF -308G>A Single Nucleotide Polymorphism Is Associated With Leprosy Among Brazilians: A Genetic Epidemiology Assessment, Meta-Analysis, and Functional Study.
- Author
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Cardoso CC, Pereira AC, Brito-de-Souza VN, Duraes SM, Ribeiro-Alves M, Augusto C Nery J, Francio AS, Vanderborght PR, Parelli FP, Alter A, Salgado JL, Sampaio EP, Santos AR, Leide Wr Oliveira M, Sarno EN, Schurr E, Mira MT, Pacheco AG, and Moraes MO
- Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2011