Association of IFN-γ +874 A/T SNP and hypermethylation of the -53 CpG site with tuberculosis susceptibility
Introduction: Tuberculosis (TB) is now the 2nd leading infectious killer after COVID-19 and the 13th leading cause of death worldwide. Moreover, TB is a lethal combination for HIV-patients. Th1 responses and particularly IFN-γ are crucial for immune protection against Mycobacterium tuberculosis infe...
| Autores: | , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2023 |
| País: | Argentina |
| Institución: | Consejo Nacional de Investigaciones Científicas y Técnicas |
| Repositorio: | CONICET Digital (CONICET) |
| Idioma: | inglés |
| OAI Identifier: | oai:ri.conicet.gov.ar:11336/212246 |
| Acceso en línea: | http://hdl.handle.net/11336/212246 |
| Access Level: | acceso abierto |
| Palabra clave: | IFNG METHYLATION SNPS SUSCEPTIBILITY TUBERCULOSIS https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
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Argentina |
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| dc.title.none.fl_str_mv |
Association of IFN-γ +874 A/T SNP and hypermethylation of the -53 CpG site with tuberculosis susceptibility |
| title |
Association of IFN-γ +874 A/T SNP and hypermethylation of the -53 CpG site with tuberculosis susceptibility |
| spellingShingle |
Association of IFN-γ +874 A/T SNP and hypermethylation of the -53 CpG site with tuberculosis susceptibility Alvarez, Guadalupe Inés IFNG METHYLATION SNPS SUSCEPTIBILITY TUBERCULOSIS https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
| title_short |
Association of IFN-γ +874 A/T SNP and hypermethylation of the -53 CpG site with tuberculosis susceptibility |
| title_full |
Association of IFN-γ +874 A/T SNP and hypermethylation of the -53 CpG site with tuberculosis susceptibility |
| title_fullStr |
Association of IFN-γ +874 A/T SNP and hypermethylation of the -53 CpG site with tuberculosis susceptibility |
| title_full_unstemmed |
Association of IFN-γ +874 A/T SNP and hypermethylation of the -53 CpG site with tuberculosis susceptibility |
| title_sort |
Association of IFN-γ +874 A/T SNP and hypermethylation of the -53 CpG site with tuberculosis susceptibility |
| dc.creator.none.fl_str_mv |
Alvarez, Guadalupe Inés Hernández del Pino, Rodrigo Emanuel Barbero, Angela Maria Estermann, Martín Andrés Celano, Josefina Musella, Rosa María Palmero, Domingo Juan García, Verónica Edith Pasquinelli, Virginia |
| author |
Alvarez, Guadalupe Inés |
| author_facet |
Alvarez, Guadalupe Inés Hernández del Pino, Rodrigo Emanuel Barbero, Angela Maria Estermann, Martín Andrés Celano, Josefina Musella, Rosa María Palmero, Domingo Juan García, Verónica Edith Pasquinelli, Virginia |
| author_role |
author |
| author2 |
Hernández del Pino, Rodrigo Emanuel Barbero, Angela Maria Estermann, Martín Andrés Celano, Josefina Musella, Rosa María Palmero, Domingo Juan García, Verónica Edith Pasquinelli, Virginia |
| author2_role |
author author author author author author author author |
| dc.subject.none.fl_str_mv |
IFNG METHYLATION SNPS SUSCEPTIBILITY TUBERCULOSIS https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
| topic |
IFNG METHYLATION SNPS SUSCEPTIBILITY TUBERCULOSIS https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
| description |
Introduction: Tuberculosis (TB) is now the 2nd leading infectious killer after COVID-19 and the 13th leading cause of death worldwide. Moreover, TB is a lethal combination for HIV-patients. Th1 responses and particularly IFN-γ are crucial for immune protection against Mycobacterium tuberculosis infection. Many gene variants for IFNG that confer susceptibility to TB have been described in multiple ethnic populations. Likewise, some epigenetic modifications have been evaluated, being CpG methylation the major epigenetic mark that makes chromatin inaccessible to transcription factors, thus avoiding the initiation of IFNG transcription. Methods: We evaluated both genetic and epigenetic changes involved in IFN-γ production and TB susceptibility in Argentine population. Amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) was performed for the IFN-γ +874 A/T polymorphism (rs2430561) genotyping in 199 healthy donors (HD) and 173 tuberculosis (TB) patients. IFN-γ levels from M. tuberculosis-stimulated PBMCs were measured by ELISA. The methylation status at the -53 CpG site of the IFNG promoter in individuals with latent infection (LTBI), TB and HD was determine by pyrosequencing. Results: Using a case-control study, we found that A allele and, consequently, AA genotype were overrepresented in patients with active disease. Moreover, HD carrying T allele (AT or TT genotype) evidenced an augmented IFN-γ secretion compared to TB patients. Codominance was the genetic model that best fits our results according to the Akaike information criterion (AIC). In addition, increased methylation levels at the -53 CpG site in the IFN-γ promoter were observed in whole blood of patients with active TB compared to LTBI individuals. Discussion: IFN-γ is regulated by genetic variants and epigenetic modifications during TB. Besides, AA genotype of the rs2430561 single nucleotide polymorphism could be considered as a potential TB susceptibility genetic biomarker in Argentina and the methylation of the -53 CpG site could result in a useful predictor of TB reactivation. |
| publishDate |
2023 |
| dc.date.none.fl_str_mv |
2023-01 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
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article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/212246 Alvarez, Guadalupe Inés; Hernández del Pino, Rodrigo Emanuel; Barbero, Angela Maria; Estermann, Martín Andrés; Celano, Josefina; et al.; Association of IFN-γ +874 A/T SNP and hypermethylation of the -53 CpG site with tuberculosis susceptibility; Frontiers Media; Frontiers in Cellular and Infection Microbiology; 13; 1-2023; 1-11 2235-2988 CONICET Digital CONICET |
| url |
http://hdl.handle.net/11336/212246 |
| identifier_str_mv |
Alvarez, Guadalupe Inés; Hernández del Pino, Rodrigo Emanuel; Barbero, Angela Maria; Estermann, Martín Andrés; Celano, Josefina; et al.; Association of IFN-γ +874 A/T SNP and hypermethylation of the -53 CpG site with tuberculosis susceptibility; Frontiers Media; Frontiers in Cellular and Infection Microbiology; 13; 1-2023; 1-11 2235-2988 CONICET Digital CONICET |
| dc.language.none.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/doi/10.3389/fcimb.2023.1080100 |
| dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
| eu_rights_str_mv |
openAccess |
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https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
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application/pdf application/pdf |
| dc.publisher.none.fl_str_mv |
Frontiers Media |
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Frontiers Media |
| dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
| instname_str |
Consejo Nacional de Investigaciones Científicas y Técnicas |
| reponame_str |
CONICET Digital (CONICET) |
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CONICET Digital (CONICET) |
| repository.name.fl_str_mv |
CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
| repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
| _version_ |
1799196306487377920 |
| spelling |
Association of IFN-γ +874 A/T SNP and hypermethylation of the -53 CpG site with tuberculosis susceptibilityAlvarez, Guadalupe InésHernández del Pino, Rodrigo EmanuelBarbero, Angela MariaEstermann, Martín AndrésCelano, JosefinaMusella, Rosa MaríaPalmero, Domingo JuanGarcía, Verónica EdithPasquinelli, VirginiaIFNGMETHYLATIONSNPSSUSCEPTIBILITYTUBERCULOSIShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Introduction: Tuberculosis (TB) is now the 2nd leading infectious killer after COVID-19 and the 13th leading cause of death worldwide. Moreover, TB is a lethal combination for HIV-patients. Th1 responses and particularly IFN-γ are crucial for immune protection against Mycobacterium tuberculosis infection. Many gene variants for IFNG that confer susceptibility to TB have been described in multiple ethnic populations. Likewise, some epigenetic modifications have been evaluated, being CpG methylation the major epigenetic mark that makes chromatin inaccessible to transcription factors, thus avoiding the initiation of IFNG transcription. Methods: We evaluated both genetic and epigenetic changes involved in IFN-γ production and TB susceptibility in Argentine population. Amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) was performed for the IFN-γ +874 A/T polymorphism (rs2430561) genotyping in 199 healthy donors (HD) and 173 tuberculosis (TB) patients. IFN-γ levels from M. tuberculosis-stimulated PBMCs were measured by ELISA. The methylation status at the -53 CpG site of the IFNG promoter in individuals with latent infection (LTBI), TB and HD was determine by pyrosequencing. Results: Using a case-control study, we found that A allele and, consequently, AA genotype were overrepresented in patients with active disease. Moreover, HD carrying T allele (AT or TT genotype) evidenced an augmented IFN-γ secretion compared to TB patients. Codominance was the genetic model that best fits our results according to the Akaike information criterion (AIC). In addition, increased methylation levels at the -53 CpG site in the IFN-γ promoter were observed in whole blood of patients with active TB compared to LTBI individuals. Discussion: IFN-γ is regulated by genetic variants and epigenetic modifications during TB. Besides, AA genotype of the rs2430561 single nucleotide polymorphism could be considered as a potential TB susceptibility genetic biomarker in Argentina and the methylation of the -53 CpG site could result in a useful predictor of TB reactivation.Fil: Alvarez, Guadalupe Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Hernández del Pino, Rodrigo Emanuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; ArgentinaFil: Barbero, Angela Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; ArgentinaFil: Estermann, Martín Andrés. Universidad Nacional del Noroeste de la Provincia de Buenos Aires; ArgentinaFil: Celano, Josefina. Universidad Nacional del Noroeste de la Provincia de Buenos Aires; ArgentinaFil: Musella, Rosa María. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Palmero, Domingo Juan. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: García, Verónica Edith. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Pasquinelli, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; ArgentinaFrontiers Media2023-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/212246Alvarez, Guadalupe Inés; Hernández del Pino, Rodrigo Emanuel; Barbero, Angela Maria; Estermann, Martín Andrés; Celano, Josefina; et al.; Association of IFN-γ +874 A/T SNP and hypermethylation of the -53 CpG site with tuberculosis susceptibility; Frontiers Media; Frontiers in Cellular and Infection Microbiology; 13; 1-2023; 1-112235-2988CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3389/fcimb.2023.1080100info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2024-05-08T14:22:31Zoai:ri.conicet.gov.ar:11336/212246instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982024-05-08 14:22:31.646CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
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15,811543 |