The -308 bp TNF gene polymorphism influences tumor necrosis factor expression in leprosy patients in Bahia State, Brazil.

Autor: Oliveira JM; National Institute of Science and Technology in Tropical Diseases, Brazil and Federal University of Bahia, Salvador, Brazil; Program of Post-graduation in Health Sciences, Federal University of Bahia, Salvador, Brazil. Electronic address: joycemouraoliveira@yahoo.com.br., Rêgo JL; National Institute of Science and Technology in Tropical Diseases, Brazil and Federal University of Bahia, Salvador, Brazil; Program of Post-graduation in Health Sciences, Federal University of Bahia, Salvador, Brazil. Electronic address: jamileao@hotmail.com., de Lima Santana N; National Institute of Science and Technology in Tropical Diseases, Brazil and Federal University of Bahia, Salvador, Brazil; Program of Post-graduation in Health Sciences, Federal University of Bahia, Salvador, Brazil. Electronic address: nlimas@hotmail.com., Braz M; National Institute of Science and Technology in Tropical Diseases, Brazil and Federal University of Bahia, Salvador, Brazil; Program of Post-graduation in Health Sciences, Federal University of Bahia, Salvador, Brazil. Electronic address: mbrazuefs@gmail.com., Jamieson SE; Telethon Kids Institute, The University of Western Australia, Subiaco, Western Australia, Australia. Electronic address: sarra.jamieson@telethonkids.org.au., Vieira TS; National Institute of Science and Technology in Tropical Diseases, Brazil and Federal University of Bahia, Salvador, Brazil. Electronic address: thaymiss@hotmail.com., Magalhães TL; National Institute of Science and Technology in Tropical Diseases, Brazil and Federal University of Bahia, Salvador, Brazil. Electronic address: thaislamegomagalhaes@gmail.com., Machado PRL; National Institute of Science and Technology in Tropical Diseases, Brazil and Federal University of Bahia, Salvador, Brazil; Program of Post-graduation in Health Sciences, Federal University of Bahia, Salvador, Brazil. Electronic address: prlmachado@uol.com.br., Blackwell JM; Telethon Kids Institute, The University of Western Australia, Subiaco, Western Australia, Australia. Electronic address: jblackwell@ichr.uws.edu.au., Castellucci LC; National Institute of Science and Technology in Tropical Diseases, Brazil and Federal University of Bahia, Salvador, Brazil; Program of Post-graduation in Health Sciences, Federal University of Bahia, Salvador, Brazil. Electronic address: leacastel@hotmail.com.
Jazyk: angličtina
Zdroj: Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases [Infect Genet Evol] 2016 Apr; Vol. 39, pp. 147-154. Date of Electronic Publication: 2016 Jan 30.
DOI: 10.1016/j.meegid.2016.01.026
Abstrakt: Leprosy or Hansen's disease is a debilitating chronic granulomatous disease caused by Mycobacterium leprae, with high incidence and prevalence in Brazil. The -308 bp G/A single nucleotide polymorphism (SNP rs1800629) in the tumor necrosis factor (TNF) gene promoter is a proposed risk factor for leprosy. In Brazil, Northern India, Egypt and Nepal, the common G allele was associated with leprosy. In Eastern India, Thailand and Malawi the minor A allele was the risk factor. Allele A was previously associated with high TNF. We genotyped rs1800629 in 326 leprosy cases from Bahia State, Brazil, including 72 paucibacillary (PB) and 47 multibacillary (MB) without reactions, and 69 reversal reaction (RR) and 78 erythema nodosum leprosum (ENL) with reactions. Logistic regression was used to compare patient groups with 331 healthy controls. Relative TNF mRNA was determined in peripheral blood leukocytes by QRTPCR, and serum TNF levels measured by ELISA. We found that TNF mRNA expression was higher (P=0.03) in leprosy patients compared to endemic controls, but did not differ significantly between clinical subgroups. Carriage of the minor A allele was associated (P=0.003) with low TNF mRNA across leprosy patients. Nevertheless, we found no evidence for either allele at this SNP as a risk factor for leprosy per se (OR=1.12, 95% CI 0.79-1.60, P=0.52), PB (OR=0.99, 95% CI 0.54-1.81, P=0.97), MB (OR=0.86, 95% CI 0.40-1.83, P=0.70), RR (OR=1.37, 95% CI 0.79-2.38, P=0.27) or ENL (OR=0.76, 95% CI 0.40-1.45, P=0.42) when compared to endemic controls. Further studies are required to determine whether the influence of the minor A allele on TNF mRNA levels determines response to treatment, particularly in the context of ENL reaction treatment with anti-TNF therapies and RR reactions where treatment with prednisolone is known to reduce TNF levels. Our findings contribute to understanding TNF as an important determinant of leprosy immunopathology in Brazil.
(Copyright © 2016 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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