Genome-wide association study analysis of single nucleotide variants in L. infantum associated with IL-6 inflammatory response in visceral leishmaniasis
Elevated levels of IL-6 in plasma are associated with the severity of visceral leishmaniasis (VL). The clinical manifestations of VL vary among patients, influenced by host factors and the virulence of the Leishmania infantum parasite. Considering that severe VL may result from an exaggerated inflam...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Cambridge University Press
|
| Series: | Parasitology |
| Subjects: | |
| Online Access: | https://www.cambridge.org/core/product/identifier/S0031182024001598/type/journal_article |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832591628801409024 |
|---|---|
| author | Amanda Miranda da Silva Kátia Silene Sousa Carvalho Caio Andrey Bezerra Januário Raquel Gomes de Sena Carneiro Caldas Bianka Lopes da Silva Paulino Débora Cavalcante Braz Dorcas Lamounier Costa Gabriel da Luz Wallau Wilson Jose da Silva Junior Carlos Henrique Nery Costa |
| author_facet | Amanda Miranda da Silva Kátia Silene Sousa Carvalho Caio Andrey Bezerra Januário Raquel Gomes de Sena Carneiro Caldas Bianka Lopes da Silva Paulino Débora Cavalcante Braz Dorcas Lamounier Costa Gabriel da Luz Wallau Wilson Jose da Silva Junior Carlos Henrique Nery Costa |
| author_sort | Amanda Miranda da Silva |
| collection | DOAJ |
| description | Elevated levels of IL-6 in plasma are associated with the severity of visceral leishmaniasis (VL). The clinical manifestations of VL vary among patients, influenced by host factors and the virulence of the Leishmania infantum parasite. Considering that severe VL may result from an exaggerated inflammatory response, this study investigated whether IL-6 could serve as a biomarker to identify pro-inflammatory virulence factors. We conducted a genome-wide association study (GWAS) analysis on L. infantum isolates from patients with VL, whose IL-6 concentrations were measured. The analysis revealed that the relationship between IL-6 levels and clinical outcomes (survival vs mortality) had an area under the curve (AUC) of 0.67 (95% CI 0.52–0.81). A cut-off of 391.7 pg mL−1 for IL-6 was established to conduct a logistic regression analysis. We identified 10 029 single nucleotide variants (SNVs) across 62 genomes, resulting in 6,948 SNVs after filtering, of which 6,341 are located in protein-coding regions. The association analysis with PLINK identified 722 variants, of which 35 showed significant associations, with odds ratios ≥3.3, primarily in coding regions. These findings demonstrate that IL-6 levels tended to be associated with the fatal outcome of VL and highlight 35 novel genetic variants that could serve as potential biomarkers for prognosis. Further research into the biological role of these variants may lead to new therapeutic targets and improve the clinical management of VL, especially in identifying high-risk patients. |
| format | Article |
| id | doaj-art-c45e30dc09d34b62abb2fed8e043bcb9 |
| institution | Kabale University |
| issn | 0031-1820 1469-8161 |
| language | English |
| publisher | Cambridge University Press |
| record_format | Article |
| series | Parasitology |
| spelling | doaj-art-c45e30dc09d34b62abb2fed8e043bcb92025-01-22T08:48:22ZengCambridge University PressParasitology0031-18201469-81611910.1017/S0031182024001598Genome-wide association study analysis of single nucleotide variants in L. infantum associated with IL-6 inflammatory response in visceral leishmaniasisAmanda Miranda da Silva0https://orcid.org/0000-0001-6476-4809Kátia Silene Sousa Carvalho1Caio Andrey Bezerra Januário2Raquel Gomes de Sena Carneiro Caldas3Bianka Lopes da Silva Paulino4Débora Cavalcante Braz5Dorcas Lamounier Costa6Gabriel da Luz Wallau7Wilson Jose da Silva Junior8Carlos Henrique Nery Costa9Postgraduate Program in Biotechnology, Northeast Network of Biotechnology, Federal University of Piauí, Piauí, Brazil Leishmaniasis Research Laboratory – LabLeish, Piauí, BrazilLeishmaniasis Research Laboratory – LabLeish, Piauí, BrazilPostgraduate Program in Genetics and Molecular Biology, Federal University of Pernambuco – UFPE, Pernambuco, BrazilPostgraduate Program in Biological Sciences, Federal University of Pernambuco – UFPE, Pernambuco, BrazilLeishmaniasis Research Laboratory – LabLeish, Piauí, BrazilPharmacy Course, Federal University of Piauí, Piauí, BrazilPostgraduate Program in Biotechnology, Northeast Network of Biotechnology, Federal University of Piauí, Piauí, Brazil Leishmaniasis Research Laboratory – LabLeish, Piauí, Brazil Natan Portella Institute of Tropical Diseases, Piauí, Brazil Center for Intelligence on Emerging and Neglected Tropical Diseases – CIATEN, Piauí, BrazilDepartment of Entomology, Instituto Aggeu Magalhães, Fundação Oswaldo Cruz – Fiocruz, Pernambuco, BrazilDepartment of Entomology, Instituto Aggeu Magalhães, Fundação Oswaldo Cruz – Fiocruz, Pernambuco, BrazilPostgraduate Program in Biotechnology, Northeast Network of Biotechnology, Federal University of Piauí, Piauí, Brazil Leishmaniasis Research Laboratory – LabLeish, Piauí, Brazil Natan Portella Institute of Tropical Diseases, Piauí, Brazil Center for Intelligence on Emerging and Neglected Tropical Diseases – CIATEN, Piauí, BrazilElevated levels of IL-6 in plasma are associated with the severity of visceral leishmaniasis (VL). The clinical manifestations of VL vary among patients, influenced by host factors and the virulence of the Leishmania infantum parasite. Considering that severe VL may result from an exaggerated inflammatory response, this study investigated whether IL-6 could serve as a biomarker to identify pro-inflammatory virulence factors. We conducted a genome-wide association study (GWAS) analysis on L. infantum isolates from patients with VL, whose IL-6 concentrations were measured. The analysis revealed that the relationship between IL-6 levels and clinical outcomes (survival vs mortality) had an area under the curve (AUC) of 0.67 (95% CI 0.52–0.81). A cut-off of 391.7 pg mL−1 for IL-6 was established to conduct a logistic regression analysis. We identified 10 029 single nucleotide variants (SNVs) across 62 genomes, resulting in 6,948 SNVs after filtering, of which 6,341 are located in protein-coding regions. The association analysis with PLINK identified 722 variants, of which 35 showed significant associations, with odds ratios ≥3.3, primarily in coding regions. These findings demonstrate that IL-6 levels tended to be associated with the fatal outcome of VL and highlight 35 novel genetic variants that could serve as potential biomarkers for prognosis. Further research into the biological role of these variants may lead to new therapeutic targets and improve the clinical management of VL, especially in identifying high-risk patients.https://www.cambridge.org/core/product/identifier/S0031182024001598/type/journal_articlegenome-wide association studygenomicsinterleukin-6Leishmania infantumvisceral leishmaniasis |
| spellingShingle | Amanda Miranda da Silva Kátia Silene Sousa Carvalho Caio Andrey Bezerra Januário Raquel Gomes de Sena Carneiro Caldas Bianka Lopes da Silva Paulino Débora Cavalcante Braz Dorcas Lamounier Costa Gabriel da Luz Wallau Wilson Jose da Silva Junior Carlos Henrique Nery Costa Genome-wide association study analysis of single nucleotide variants in L. infantum associated with IL-6 inflammatory response in visceral leishmaniasis Parasitology genome-wide association study genomics interleukin-6 Leishmania infantum visceral leishmaniasis |
| title | Genome-wide association study analysis of single nucleotide variants in L. infantum associated with IL-6 inflammatory response in visceral leishmaniasis |
| title_full | Genome-wide association study analysis of single nucleotide variants in L. infantum associated with IL-6 inflammatory response in visceral leishmaniasis |
| title_fullStr | Genome-wide association study analysis of single nucleotide variants in L. infantum associated with IL-6 inflammatory response in visceral leishmaniasis |
| title_full_unstemmed | Genome-wide association study analysis of single nucleotide variants in L. infantum associated with IL-6 inflammatory response in visceral leishmaniasis |
| title_short | Genome-wide association study analysis of single nucleotide variants in L. infantum associated with IL-6 inflammatory response in visceral leishmaniasis |
| title_sort | genome wide association study analysis of single nucleotide variants in l infantum associated with il 6 inflammatory response in visceral leishmaniasis |
| topic | genome-wide association study genomics interleukin-6 Leishmania infantum visceral leishmaniasis |
| url | https://www.cambridge.org/core/product/identifier/S0031182024001598/type/journal_article |
| work_keys_str_mv | AT amandamirandadasilva genomewideassociationstudyanalysisofsinglenucleotidevariantsinlinfantumassociatedwithil6inflammatoryresponseinvisceralleishmaniasis AT katiasilenesousacarvalho genomewideassociationstudyanalysisofsinglenucleotidevariantsinlinfantumassociatedwithil6inflammatoryresponseinvisceralleishmaniasis AT caioandreybezerrajanuario genomewideassociationstudyanalysisofsinglenucleotidevariantsinlinfantumassociatedwithil6inflammatoryresponseinvisceralleishmaniasis AT raquelgomesdesenacarneirocaldas genomewideassociationstudyanalysisofsinglenucleotidevariantsinlinfantumassociatedwithil6inflammatoryresponseinvisceralleishmaniasis AT biankalopesdasilvapaulino genomewideassociationstudyanalysisofsinglenucleotidevariantsinlinfantumassociatedwithil6inflammatoryresponseinvisceralleishmaniasis AT deboracavalcantebraz genomewideassociationstudyanalysisofsinglenucleotidevariantsinlinfantumassociatedwithil6inflammatoryresponseinvisceralleishmaniasis AT dorcaslamouniercosta genomewideassociationstudyanalysisofsinglenucleotidevariantsinlinfantumassociatedwithil6inflammatoryresponseinvisceralleishmaniasis AT gabrieldaluzwallau genomewideassociationstudyanalysisofsinglenucleotidevariantsinlinfantumassociatedwithil6inflammatoryresponseinvisceralleishmaniasis AT wilsonjosedasilvajunior genomewideassociationstudyanalysisofsinglenucleotidevariantsinlinfantumassociatedwithil6inflammatoryresponseinvisceralleishmaniasis AT carloshenriquenerycosta genomewideassociationstudyanalysisofsinglenucleotidevariantsinlinfantumassociatedwithil6inflammatoryresponseinvisceralleishmaniasis |