Variants of MIRNA146A rs2910164 and MIRNA499 rs3746444 are associated with the development of cutaneous leishmaniasis caused by Leishmania guyanensis and with plasma chemokine IL-8.

Leishmania are intracellular protozoan parasites that cause a wide spectrum of clinical manifestations in genetically susceptible individuals with an insufficient or balanced Th1 immune response to eliminate the parasite. MiRNAs play important regulatory role in numerous biological processes includi...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: 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
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2021
Materias:
Acceso en línea:https://doaj.org/article/04dded1909ba430584690d690bcb8879
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:04dded1909ba430584690d690bcb8879
record_format dspace
spelling oai:doaj.org-article:04dded1909ba430584690d690bcb88792021-12-02T20:24:05ZVariants of MIRNA146A rs2910164 and MIRNA499 rs3746444 are associated with the development of cutaneous leishmaniasis caused by Leishmania guyanensis and with plasma chemokine IL-8.1935-27271935-273510.1371/journal.pntd.0009795https://doaj.org/article/04dded1909ba430584690d690bcb88792021-09-01T00:00:00Zhttps://doi.org/10.1371/journal.pntd.0009795https://doaj.org/toc/1935-2727https://doaj.org/toc/1935-2735Leishmania are intracellular protozoan parasites that cause a wide spectrum of clinical manifestations in genetically susceptible individuals with an insufficient or balanced Th1 immune response to eliminate the parasite. MiRNAs play important regulatory role in numerous biological processes including essential cellular functions. miR146-a acts as an inhibitor of interleukin 1 receptor associated kinase 1 (IRAK1) and tumour necrosis factor (TNF) receptor associated factor 6 (TRAF6) present in the toll-like receptors pathway while miR499a modulates TGF-β and TNF signalling pathways. Here, we investigated whether MIRNA146A rs2910164 and MIRNA499 rs3746444 variants are associated with the development of L. guyanensis (Lg)-cutaneous leishmaniasis (CL). The variants MIR146A rs2910164 and MIR499A rs3746444 were assessed in 850 patients with Lg-CL and 891 healthy controls by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Plasma cytokines were measured using the BioPlex assay. Carriers of rs2910164 CC genotype have 30% higher odds of developing CL (ORadjage/sex = 1.3 [95%CI 0.9-1.8]; Padjage/sex 0.14) compared to individuals with the genotype GG (ORadjage/sex = 0.77 [95%CI 0.56-1.0]; Padjage/sex 0.14) if exposed to Lg-infection. Heterozygous GC individuals also showed lower odds of developing CL (ORadjage/sex = 0.77 [95%CI 0.5-1.1]; Padjage/sex 0.09). Homozygosity for the allele C is suggestive of an association with the development of Lg-CL among exposed individuals to Lg-infection. However, the odds of developing CL associated with the CC genotype was evident only in male individuals (ORadjage = 1.3 [95% CI = 0.9-2.0]; Padjage = 0.06). Individuals homozygous for the G allele tend to have higher plasma IL-8 and CCL5. Similarly, for the MIR499A rs3746444, an association with the G allele was only observed among male individuals (OR = 1.4 [1.0-1.9]; P = 0.009). In a dominant model, individuals with the G allele (GG-GA) when compared to the AA genotype reveals that carriers of the G allele have 40% elevated odds of developing Lg-CL (ORadjage = 1.4 [1.1-1.9]). Individuals with the GG genotype have higher odds of developing Lg-CL (ORadjage/sex = 2.0 [95%CI 0.83-5.0]; Padjage = 0.01. Individuals homozygous for the G allele have higher plasma IL-8. Genetic combinations of both variants revealed that male individuals exposed to Lg bearing three or four susceptible alleles have higher odds of developing Lg-CL (OR = 2.3 [95% CI 1.0-4.7]; p = 0.017). Both MIR146A rs2910164 and MIR499A rs3746444 are associated with the development of Lg-CL and this association is prevalent in male individuals.Tirza Gabrielle Ramos de MesquitaJosé do Espírito Santo JuniorThais Carneiro de LacerdaKrys Layane Guimarães Duarte QueirozCláudio Marcello da Silveira JúniorJosé Pereira de Moura NetoLissianne Augusta Matos GomesMara Lúcia Gomes de SouzaMarcus Vinitius de Farias GuerraRajendranath RamasawmyPublic Library of Science (PLoS)articleArctic medicine. Tropical medicineRC955-962Public aspects of medicineRA1-1270ENPLoS Neglected Tropical Diseases, Vol 15, Iss 9, p e0009795 (2021)
institution DOAJ
collection DOAJ
language EN
topic Arctic medicine. Tropical medicine
RC955-962
Public aspects of medicine
RA1-1270
spellingShingle Arctic medicine. Tropical medicine
RC955-962
Public aspects of medicine
RA1-1270
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
Variants of MIRNA146A rs2910164 and MIRNA499 rs3746444 are associated with the development of cutaneous leishmaniasis caused by Leishmania guyanensis and with plasma chemokine IL-8.
description Leishmania are intracellular protozoan parasites that cause a wide spectrum of clinical manifestations in genetically susceptible individuals with an insufficient or balanced Th1 immune response to eliminate the parasite. MiRNAs play important regulatory role in numerous biological processes including essential cellular functions. miR146-a acts as an inhibitor of interleukin 1 receptor associated kinase 1 (IRAK1) and tumour necrosis factor (TNF) receptor associated factor 6 (TRAF6) present in the toll-like receptors pathway while miR499a modulates TGF-β and TNF signalling pathways. Here, we investigated whether MIRNA146A rs2910164 and MIRNA499 rs3746444 variants are associated with the development of L. guyanensis (Lg)-cutaneous leishmaniasis (CL). The variants MIR146A rs2910164 and MIR499A rs3746444 were assessed in 850 patients with Lg-CL and 891 healthy controls by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Plasma cytokines were measured using the BioPlex assay. Carriers of rs2910164 CC genotype have 30% higher odds of developing CL (ORadjage/sex = 1.3 [95%CI 0.9-1.8]; Padjage/sex 0.14) compared to individuals with the genotype GG (ORadjage/sex = 0.77 [95%CI 0.56-1.0]; Padjage/sex 0.14) if exposed to Lg-infection. Heterozygous GC individuals also showed lower odds of developing CL (ORadjage/sex = 0.77 [95%CI 0.5-1.1]; Padjage/sex 0.09). Homozygosity for the allele C is suggestive of an association with the development of Lg-CL among exposed individuals to Lg-infection. However, the odds of developing CL associated with the CC genotype was evident only in male individuals (ORadjage = 1.3 [95% CI = 0.9-2.0]; Padjage = 0.06). Individuals homozygous for the G allele tend to have higher plasma IL-8 and CCL5. Similarly, for the MIR499A rs3746444, an association with the G allele was only observed among male individuals (OR = 1.4 [1.0-1.9]; P = 0.009). In a dominant model, individuals with the G allele (GG-GA) when compared to the AA genotype reveals that carriers of the G allele have 40% elevated odds of developing Lg-CL (ORadjage = 1.4 [1.1-1.9]). Individuals with the GG genotype have higher odds of developing Lg-CL (ORadjage/sex = 2.0 [95%CI 0.83-5.0]; Padjage = 0.01. Individuals homozygous for the G allele have higher plasma IL-8. Genetic combinations of both variants revealed that male individuals exposed to Lg bearing three or four susceptible alleles have higher odds of developing Lg-CL (OR = 2.3 [95% CI 1.0-4.7]; p = 0.017). Both MIR146A rs2910164 and MIR499A rs3746444 are associated with the development of Lg-CL and this association is prevalent in male individuals.
format article
author 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
author_facet 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
author_sort Tirza Gabrielle Ramos de Mesquita
title Variants of MIRNA146A rs2910164 and MIRNA499 rs3746444 are associated with the development of cutaneous leishmaniasis caused by Leishmania guyanensis and with plasma chemokine IL-8.
title_short Variants of MIRNA146A rs2910164 and MIRNA499 rs3746444 are associated with the development of cutaneous leishmaniasis caused by Leishmania guyanensis and with plasma chemokine IL-8.
title_full Variants of MIRNA146A rs2910164 and MIRNA499 rs3746444 are associated with the development of cutaneous leishmaniasis caused by Leishmania guyanensis and with plasma chemokine IL-8.
title_fullStr Variants of MIRNA146A rs2910164 and MIRNA499 rs3746444 are associated with the development of cutaneous leishmaniasis caused by Leishmania guyanensis and with plasma chemokine IL-8.
title_full_unstemmed Variants of MIRNA146A rs2910164 and MIRNA499 rs3746444 are associated with the development of cutaneous leishmaniasis caused by Leishmania guyanensis and with plasma chemokine IL-8.
title_sort variants of mirna146a rs2910164 and mirna499 rs3746444 are associated with the development of cutaneous leishmaniasis caused by leishmania guyanensis and with plasma chemokine il-8.
publisher Public Library of Science (PLoS)
publishDate 2021
url https://doaj.org/article/04dded1909ba430584690d690bcb8879
work_keys_str_mv AT tirzagabrielleramosdemesquita variantsofmirna146ars2910164andmirna499rs3746444areassociatedwiththedevelopmentofcutaneousleishmaniasiscausedbyleishmaniaguyanensisandwithplasmachemokineil8
AT josedoespiritosantojunior variantsofmirna146ars2910164andmirna499rs3746444areassociatedwiththedevelopmentofcutaneousleishmaniasiscausedbyleishmaniaguyanensisandwithplasmachemokineil8
AT thaiscarneirodelacerda variantsofmirna146ars2910164andmirna499rs3746444areassociatedwiththedevelopmentofcutaneousleishmaniasiscausedbyleishmaniaguyanensisandwithplasmachemokineil8
AT kryslayaneguimaraesduartequeiroz variantsofmirna146ars2910164andmirna499rs3746444areassociatedwiththedevelopmentofcutaneousleishmaniasiscausedbyleishmaniaguyanensisandwithplasmachemokineil8
AT claudiomarcellodasilveirajunior variantsofmirna146ars2910164andmirna499rs3746444areassociatedwiththedevelopmentofcutaneousleishmaniasiscausedbyleishmaniaguyanensisandwithplasmachemokineil8
AT josepereirademouraneto variantsofmirna146ars2910164andmirna499rs3746444areassociatedwiththedevelopmentofcutaneousleishmaniasiscausedbyleishmaniaguyanensisandwithplasmachemokineil8
AT lissianneaugustamatosgomes variantsofmirna146ars2910164andmirna499rs3746444areassociatedwiththedevelopmentofcutaneousleishmaniasiscausedbyleishmaniaguyanensisandwithplasmachemokineil8
AT maraluciagomesdesouza variantsofmirna146ars2910164andmirna499rs3746444areassociatedwiththedevelopmentofcutaneousleishmaniasiscausedbyleishmaniaguyanensisandwithplasmachemokineil8
AT marcusvinitiusdefariasguerra variantsofmirna146ars2910164andmirna499rs3746444areassociatedwiththedevelopmentofcutaneousleishmaniasiscausedbyleishmaniaguyanensisandwithplasmachemokineil8
AT rajendranathramasawmy variantsofmirna146ars2910164andmirna499rs3746444areassociatedwiththedevelopmentofcutaneousleishmaniasiscausedbyleishmaniaguyanensisandwithplasmachemokineil8
_version_ 1718374030392688640