BACKGROUND: Interferon-γ (IFN-γ) plays an important role in the control of Leishmania infection. Blockade of IFN-γ signaling in mice increases lesion size and parasite load. In endemic areas of Leishmaniasis, only a fraction of the population develop the disease. This suggest that host genetics may play a role in this response. We investigated whether single nucleotide polymorphisms (SNPs) in IFNG may be associated with elevated or decrease risk in the development of cutaneous leishmaniasis (CL). METHODS: We assessed 9 SNP and cytosine-adenine (CA) repeats in IFNG by nucleotide sequencing in 647 patients with CL caused by Leishmania guyanensis and 629 controls. Circulating plasma IFN-γ levels were also assayed in 400 patients with CL and 400 controls. RESULTS: The rs2069705TT genotype is associated with elevated risk of developing CL compared with the rs2069705CC genotype (OR, 1.7; 95% CI, 1.3-2.4; P = .0008). There is a 70% chance that this genotype raises the risk of developing CL. In a dominant model, carriers of the rs2069705T allele compared with the rs2069705CC genotype showed a 50% (range, 20-100%) increased risk of developing CL (OR, 1.5; 95% CI, 1.2-2.0; P = .0004). Haplotype analysis showed 1 haplotype (H1) associated with low levels of IFN-γ presented an increased risk of 60% of developing CL (OR, 1.6; 95% CI, 1.3-1.9; P = 5 × 10-5) compared with non-H1. CONCLUSIONS: IFNG variant rs2069705 seems to be a genetic modifier of clinical outcome of Leishmania infection; individuals with the H1 haplotype, associated with low levels of IFN-γ, have a 60% risk of developing CL.
BACKGROUND: Interferon-γ (IFN-γ) plays an important role in the control of Leishmania infection. Blockade of IFN-γ signaling in mice increases lesion size and parasite load. In endemic areas of Leishmaniasis, only a fraction of the population develop the disease. This suggest that host genetics may play a role in this response. We investigated whether single nucleotide polymorphisms (SNPs) in IFNG may be associated with elevated or decrease risk in the development of cutaneous leishmaniasis (CL). METHODS: We assessed 9 SNP and cytosine-adenine (CA) repeats in IFNG by nucleotide sequencing in 647 patients with CL caused by Leishmania guyanensis and 629 controls. Circulating plasma IFN-γ levels were also assayed in 400 patients with CL and 400 controls. RESULTS: The rs2069705TT genotype is associated with elevated risk of developing CL compared with the rs2069705CC genotype (OR, 1.7; 95% CI, 1.3-2.4; P = .0008). There is a 70% chance that this genotype raises the risk of developing CL. In a dominant model, carriers of the rs2069705T allele compared with the rs2069705CC genotype showed a 50% (range, 20-100%) increased risk of developing CL (OR, 1.5; 95% CI, 1.2-2.0; P = .0004). Haplotype analysis showed 1 haplotype (H1) associated with low levels of IFN-γ presented an increased risk of 60% of developing CL (OR, 1.6; 95% CI, 1.3-1.9; P = 5 × 10-5) compared with non-H1. CONCLUSIONS: IFNG variant rs2069705 seems to be a genetic modifier of clinical outcome of Leishmania infection; individuals with the H1 haplotype, associated with low levels of IFN-γ, have a 60% risk of developing CL.
Authors: José do Espírito Santo Júnior; Tirza Gabrielle Ramos de Mesquita; Luan Diego Oliveira da Silva; Felipe Jules de Araújo; Josué Lacerda de Souza; Thaís Carneiro de Lacerda; Lener Santos da Silva; Cláudio Marcello da Silveira Júnior; Krys Layane Guimarães Duarte Queiroz; Diogo Matos Dos Santos; Cilana Chagas da Silva; Héctor David Graterol Sequera; Melissa Tamayo Hermida; Mara Lúcia Gomes de Souza; Marcus Vinitius de Farias Guerra; Rajendranath Ramasawmy Journal: Pathogens Date: 2021-04-20
Authors: Tirza Gabrielle Ramos de Mesquita; José do Espírito Santo Junior; Thais Carneiro de Lacerda; Krys Layane Guimarães Duarte Queiroz; Cláudio Marcello da Silveira Júnior; José Pereira de Moura Neto; Lissianne Augusta Matos Gomes; Mara Lúcia Gomes de Souza; Marcus Vinitius de Farias Guerra; Rajendranath Ramasawmy Journal: PLoS Negl Trop Dis Date: 2021-09-20
Authors: Tirza Gabrielle Ramos de Mesquita; José do Espírito Santo Junior; Luan Diego Oliveira da Silva; George Allan Villarouco Silva; Felipe Jules de Araújo; Suzana Kanawati Pinheiro; Herllon Karllos Athaydes Kerr; Lener Santos da Silva; Luciane Macedo de Souza; Samir Assad de Almeida; Krys Layane Guimarães Duarte Queiroz; Josué Lacerda de Souza; Cilana Chagas da Silva; Héctor David Graterol Sequera; Mara Lúcia Gomes de Souza; Anderson Nogueira Barbosa; Gemilson Soares Pontes; Marcus Vinitius de Farias Guerra; Rajendranath Ramasawmy Journal: Front Immunol Date: 2022-08-25 Impact factor: 8.786
Authors: Léa C Castellucci; Lucas Almeida; Svetlana Cherlin; Michaela Fakiola; Richard W Francis; Edgar M Carvalho; Anadílton Santos da Hora; Tainã Souza do Lago; Amanda B Figueiredo; Clara M Cavalcanti; Natalia S Alves; Katia L P Morais; Andréa Teixeira-Carvalho; Walderez O Dutra; Kenneth J Gollob; Heather J Cordell; Jenefer M Blackwell Journal: Clin Infect Dis Date: 2021-05-18 Impact factor: 9.079