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Title: A genetic variant in the TRAF1/C5 gene lead susceptibility to active pulmonary tuberculosis by decreased TNF-α levels
Authors: Souza de Lima, Dhêmerson
Fadoul de Brito, Carolina
Cavalcante Barbosa, Aguyda Rayany
Brasil de Andrade Figueira, Mariana
Maciel Bonet, Julio César
Walzer, Joseph
Ramasawmy, Rajendranath
Ogusku, Mauricio Morishi
Sadahiro, Aya
Boechat, Antonio Luiz
Issue Date: 2021
metadata.dc.publisher.journal: Microbial Pathogenesis
metadata.dc.relation.ispartof: Volume 159, Número 159
Abstract: Host genetics are important to consider in the role of resistance or susceptibility for developing active pulmonary tuberculosis (TB). Several association studies have reported the role of variants in STAT4 and TRAF1/C5 as risk factors to autoimmune diseases. Nevertheless, more data is needed to elucidate the role of these gene variants in infectious disease. Our data reports for the first time, variant rs10818488 in the TRAF1/C5 gene (found 47% of the population worldwide), is associated with susceptibility (OR = 1.51) to development TB. Multivariate analysis evidenced association between rs10818488 TRAF1/C5 and risk to multibacillary TB (OR = 4.18), confers increased bacteria load in the lung, indicates a decreased ability to control pathogen levels in the lung, and spread of the pathogen to new hosts. We showed that the “loss-of-function” variant in TRAF1/C5 led to susceptibility for TB by decreased production of TNF-α. Our results suggest the role of variant TRAF1/C5 in susceptibility to TB as well as in clinical presentation of multibacillary TB. © 2021 Elsevier Ltd
metadata.dc.identifier.doi: 10.1016/j.micpath.2021.105117
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