TNF-308G > A Single Nucleotide Polymorphism Is Associated With Leprosy Among Brazilians: A Genetic Epidemiology Assessment, Meta-Analysis, and Functional Study
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2011-10-15
Autores
Cardoso, Cynthia C.
Pereira, Ana Carla
Brito-de-Souza, Vania N.
Duraes, Sandra M. B.
Ribeiro-Alves, Marcelo
Nery, Jose Augusto C.
Francio, Angela S.
Vanderborght, Patricia R.
Parelli, Francisco P. C. [UNESP]
Alter, Andrea
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Oxford University Press
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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.
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Journal of Infectious Diseases. Cary: Oxford Univ Press Inc, v. 204, n. 8, p. 1256-1263, 2011.