Single-nucleotide polymorphisms in genes associated with the vitamin D pathway related to clinical and therapeutic outcomes of American tegumentary leishmaniasis
BackgroundThe vitamin D pathway contributes to the microbicidal activity of macrophages against Leishmania infection. In addition to induction of this pathway, interferon-gamma (IFNγ), interleukin (IL)-15, and IL32γ are part of a network of pro-inflammatory cytokines. The aim of this study was to ev...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-01-01
|
| Series: | Frontiers in Cellular and Infection Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2024.1487255/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841555128775081984 |
|---|---|
| author | Iara Barreto Neves Oliveira Ramon Vieira Nunes Vanessa Rafaela Milhomem Cruz Leite Camila Freire Araújo Murilo Barros Silveira Sebastião Alves Pinto Lorena Andrade Lamounier Clayton Luiz Borges Edésio Martins Iane de Oliveira Pires Porto Rodrigo Saar Gomes Fátima Ribeiro-Dias |
| author_facet | Iara Barreto Neves Oliveira Ramon Vieira Nunes Vanessa Rafaela Milhomem Cruz Leite Camila Freire Araújo Murilo Barros Silveira Sebastião Alves Pinto Lorena Andrade Lamounier Clayton Luiz Borges Edésio Martins Iane de Oliveira Pires Porto Rodrigo Saar Gomes Fátima Ribeiro-Dias |
| author_sort | Iara Barreto Neves Oliveira |
| collection | DOAJ |
| description | BackgroundThe vitamin D pathway contributes to the microbicidal activity of macrophages against Leishmania infection. In addition to induction of this pathway, interferon-gamma (IFNγ), interleukin (IL)-15, and IL32γ are part of a network of pro-inflammatory cytokines. The aim of this study was to evaluate single-nucleotide polymorphisms (SNPs) in the components of the vitamin D pathway and associated cytokine genes that could be related to resistance or susceptibility to American tegumentary leishmaniasis (ATL).MethodsThe expressions of IFNG, IL15, IL32, CYP27B1, VDR, and other pro-inflammatory cytokines TNF, IL6, and IL17 genes were evaluated using real-time polymerase chain reaction (qPCR) in lesions of patients with localized cutaneous leishmaniasis (LCL) or mucosal leishmaniasis (ML). SNP genotypes/alleles (in IL15, IL32, CYP27B1, and VDR) were evaluated by TaqMan PCR assays using DNA from the blood of patients and healthy individuals. Serum vitamin D levels were determined by chemiluminescence.ResultsVitamin D pathway-associated genes were expressed in cutaneous as well as mucosal lesions. IFNG, IL6, and IL17 were more highly expressed in ML than in LCL. In contrast, IL32γ/CYP27B1/VDR mRNAs were mainly correlated in LCL, and IL32γ in ML makes strong connections with all cytokines. The SNP IL32 rs1555001 was less frequent in patients with ML. In addition, some SNPs appear to influence the VDR and CYP27B1 (IL15 rs10519613 and IL15 rs3775597) and IL6 (VDR rs7975232) expressions in LCL and the IL17 expression in ML (IL15 rs3775597). Gene expression was also correlated with clinical parameters, such as number of lesions (CYP27B1 mRNA) and treatment failure (VDR mRNA). In addition, one SNP was associated with treatment failure in ML (VDR rs7975232).ConclusionsOur findings suggested that some SNPs in the vitamin D pathway-associated genes can be related to resistance and therapeutic outcomes of ATL. They are promising candidates that need to be further evaluated to understand their biological effects in the control or immunopathogenesis of ATL. |
| format | Article |
| id | doaj-art-f49c825a7adf4893a99bcc82feedaa13 |
| institution | Kabale University |
| issn | 2235-2988 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj-art-f49c825a7adf4893a99bcc82feedaa132025-01-08T06:11:57ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882025-01-011410.3389/fcimb.2024.14872551487255Single-nucleotide polymorphisms in genes associated with the vitamin D pathway related to clinical and therapeutic outcomes of American tegumentary leishmaniasisIara Barreto Neves Oliveira0Ramon Vieira Nunes1Vanessa Rafaela Milhomem Cruz Leite2Camila Freire Araújo3Murilo Barros Silveira4Sebastião Alves Pinto5Lorena Andrade Lamounier6Clayton Luiz Borges7Edésio Martins8Iane de Oliveira Pires Porto9Rodrigo Saar Gomes10Fátima Ribeiro-Dias11Laboratório de Imunidade Natural (LIN), Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Goiás, BrazilLaboratório de Imunidade Natural (LIN), Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Goiás, BrazilLaboratório de Biologia Molecular (LBM), Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Goiás, BrazilDepartment of Infectious Diseases, Hospital de Doenças Tropicais Dr. Anuar Auad, Goiânia, Goiás, BrazilLaboratório de Imunidade Natural (LIN), Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Goiás, BrazilDepartment of Anatomopathology, Instituto Goiano de Oncologia e Hematologia (INGOH), Goiânia, Goiás, BrazilDepartment of Dermatology, Clínica São Braz, Goiânia, BrazilLaboratório de Biologia Molecular (LBM), Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Goiás, BrazilDepartment of Morphofunctional Axis, Universidade de Rio Verde, Goiânia, Goiás, BrazilDepartment of Morphofunctional Axis, Universidade de Rio Verde, Goiânia, Goiás, BrazilLaboratório de Imunidade Natural (LIN), Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Goiás, BrazilLaboratório de Imunidade Natural (LIN), Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Goiás, BrazilBackgroundThe vitamin D pathway contributes to the microbicidal activity of macrophages against Leishmania infection. In addition to induction of this pathway, interferon-gamma (IFNγ), interleukin (IL)-15, and IL32γ are part of a network of pro-inflammatory cytokines. The aim of this study was to evaluate single-nucleotide polymorphisms (SNPs) in the components of the vitamin D pathway and associated cytokine genes that could be related to resistance or susceptibility to American tegumentary leishmaniasis (ATL).MethodsThe expressions of IFNG, IL15, IL32, CYP27B1, VDR, and other pro-inflammatory cytokines TNF, IL6, and IL17 genes were evaluated using real-time polymerase chain reaction (qPCR) in lesions of patients with localized cutaneous leishmaniasis (LCL) or mucosal leishmaniasis (ML). SNP genotypes/alleles (in IL15, IL32, CYP27B1, and VDR) were evaluated by TaqMan PCR assays using DNA from the blood of patients and healthy individuals. Serum vitamin D levels were determined by chemiluminescence.ResultsVitamin D pathway-associated genes were expressed in cutaneous as well as mucosal lesions. IFNG, IL6, and IL17 were more highly expressed in ML than in LCL. In contrast, IL32γ/CYP27B1/VDR mRNAs were mainly correlated in LCL, and IL32γ in ML makes strong connections with all cytokines. The SNP IL32 rs1555001 was less frequent in patients with ML. In addition, some SNPs appear to influence the VDR and CYP27B1 (IL15 rs10519613 and IL15 rs3775597) and IL6 (VDR rs7975232) expressions in LCL and the IL17 expression in ML (IL15 rs3775597). Gene expression was also correlated with clinical parameters, such as number of lesions (CYP27B1 mRNA) and treatment failure (VDR mRNA). In addition, one SNP was associated with treatment failure in ML (VDR rs7975232).ConclusionsOur findings suggested that some SNPs in the vitamin D pathway-associated genes can be related to resistance and therapeutic outcomes of ATL. They are promising candidates that need to be further evaluated to understand their biological effects in the control or immunopathogenesis of ATL.https://www.frontiersin.org/articles/10.3389/fcimb.2024.1487255/fullsingle nucleotide polymorphismvitamin D receptorinterleukin-32CYP27B1interleukin-15Leishmania (Viannia) |
| spellingShingle | Iara Barreto Neves Oliveira Ramon Vieira Nunes Vanessa Rafaela Milhomem Cruz Leite Camila Freire Araújo Murilo Barros Silveira Sebastião Alves Pinto Lorena Andrade Lamounier Clayton Luiz Borges Edésio Martins Iane de Oliveira Pires Porto Rodrigo Saar Gomes Fátima Ribeiro-Dias Single-nucleotide polymorphisms in genes associated with the vitamin D pathway related to clinical and therapeutic outcomes of American tegumentary leishmaniasis Frontiers in Cellular and Infection Microbiology single nucleotide polymorphism vitamin D receptor interleukin-32 CYP27B1 interleukin-15 Leishmania (Viannia) |
| title | Single-nucleotide polymorphisms in genes associated with the vitamin D pathway related to clinical and therapeutic outcomes of American tegumentary leishmaniasis |
| title_full | Single-nucleotide polymorphisms in genes associated with the vitamin D pathway related to clinical and therapeutic outcomes of American tegumentary leishmaniasis |
| title_fullStr | Single-nucleotide polymorphisms in genes associated with the vitamin D pathway related to clinical and therapeutic outcomes of American tegumentary leishmaniasis |
| title_full_unstemmed | Single-nucleotide polymorphisms in genes associated with the vitamin D pathway related to clinical and therapeutic outcomes of American tegumentary leishmaniasis |
| title_short | Single-nucleotide polymorphisms in genes associated with the vitamin D pathway related to clinical and therapeutic outcomes of American tegumentary leishmaniasis |
| title_sort | single nucleotide polymorphisms in genes associated with the vitamin d pathway related to clinical and therapeutic outcomes of american tegumentary leishmaniasis |
| topic | single nucleotide polymorphism vitamin D receptor interleukin-32 CYP27B1 interleukin-15 Leishmania (Viannia) |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2024.1487255/full |
| work_keys_str_mv | AT iarabarretonevesoliveira singlenucleotidepolymorphismsingenesassociatedwiththevitamindpathwayrelatedtoclinicalandtherapeuticoutcomesofamericantegumentaryleishmaniasis AT ramonvieiranunes singlenucleotidepolymorphismsingenesassociatedwiththevitamindpathwayrelatedtoclinicalandtherapeuticoutcomesofamericantegumentaryleishmaniasis AT vanessarafaelamilhomemcruzleite singlenucleotidepolymorphismsingenesassociatedwiththevitamindpathwayrelatedtoclinicalandtherapeuticoutcomesofamericantegumentaryleishmaniasis AT camilafreirearaujo singlenucleotidepolymorphismsingenesassociatedwiththevitamindpathwayrelatedtoclinicalandtherapeuticoutcomesofamericantegumentaryleishmaniasis AT murilobarrossilveira singlenucleotidepolymorphismsingenesassociatedwiththevitamindpathwayrelatedtoclinicalandtherapeuticoutcomesofamericantegumentaryleishmaniasis AT sebastiaoalvespinto singlenucleotidepolymorphismsingenesassociatedwiththevitamindpathwayrelatedtoclinicalandtherapeuticoutcomesofamericantegumentaryleishmaniasis AT lorenaandradelamounier singlenucleotidepolymorphismsingenesassociatedwiththevitamindpathwayrelatedtoclinicalandtherapeuticoutcomesofamericantegumentaryleishmaniasis AT claytonluizborges singlenucleotidepolymorphismsingenesassociatedwiththevitamindpathwayrelatedtoclinicalandtherapeuticoutcomesofamericantegumentaryleishmaniasis AT edesiomartins singlenucleotidepolymorphismsingenesassociatedwiththevitamindpathwayrelatedtoclinicalandtherapeuticoutcomesofamericantegumentaryleishmaniasis AT ianedeoliveirapiresporto singlenucleotidepolymorphismsingenesassociatedwiththevitamindpathwayrelatedtoclinicalandtherapeuticoutcomesofamericantegumentaryleishmaniasis AT rodrigosaargomes singlenucleotidepolymorphismsingenesassociatedwiththevitamindpathwayrelatedtoclinicalandtherapeuticoutcomesofamericantegumentaryleishmaniasis AT fatimaribeirodias singlenucleotidepolymorphismsingenesassociatedwiththevitamindpathwayrelatedtoclinicalandtherapeuticoutcomesofamericantegumentaryleishmaniasis |