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Association of the STAT4 Gene rs7574865 Polymorphism with IFN-γ Levels in Patients with Systemic Lupus Erythematosus
STAT4 plays an important role in disease activity in SLE patients. STAT4 particles have the capacity to activate the transcription of genes associated with the production of TH1 and Th17 lymphocytes, with a greater predominance on the production of IFN-γ and IL-17A. The presence of variants in STAT4...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10048585/ https://www.ncbi.nlm.nih.gov/pubmed/36980810 http://dx.doi.org/10.3390/genes14030537 |
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author | Esparza Guerrero, Yussef Vazquez Villegas, Maria Luisa Nava Valdivia, Cesar Arturo Ponce Guarneros, Juan Manuel Perez Guerrero, Edsaul Emilio Gomez Ramirez, Eli Efrain Ramirez Villafaña, Melissa Contreras Haro, Betsabe Martinez Hernandez, Alejandra Cardona Muñoz, Ernesto German Nuño Arana, Ismael Gallardo Moya, Sergio Gabriel Celis, Alfredo Gonzalez Lopez, Laura Gamez Nava, Jorge Ivan Saldaña Cruz, Ana Miriam |
author_facet | Esparza Guerrero, Yussef Vazquez Villegas, Maria Luisa Nava Valdivia, Cesar Arturo Ponce Guarneros, Juan Manuel Perez Guerrero, Edsaul Emilio Gomez Ramirez, Eli Efrain Ramirez Villafaña, Melissa Contreras Haro, Betsabe Martinez Hernandez, Alejandra Cardona Muñoz, Ernesto German Nuño Arana, Ismael Gallardo Moya, Sergio Gabriel Celis, Alfredo Gonzalez Lopez, Laura Gamez Nava, Jorge Ivan Saldaña Cruz, Ana Miriam |
author_sort | Esparza Guerrero, Yussef |
collection | PubMed |
description | STAT4 plays an important role in disease activity in SLE patients. STAT4 particles have the capacity to activate the transcription of genes associated with the production of TH1 and Th17 lymphocytes, with a greater predominance on the production of IFN-γ and IL-17A. The presence of variants in STAT4 genes has a major impact on the generation of autoimmunity. However, there are few studies evaluating the impact of these variants on the production of proinflammatory cytokines such as IFN-γ and IL-17A. Methods—A case–control study was carried out with 206 Mexican mestizo patients residing in Western Mexico with a diagnosis of SLE and a group of 80 patients without autoimmune diseases was captured to determine the cut-off point for high IFN-γ levels. In this study, SLE patients with high IFN-γ levels were considered as cases (cut-off > 15.6 pg/mL), and SLE patients with normal IFN-γ levels were considered as controls (cut-off ≤ 15.6 pg/mL). Disease activity was identified from the systemic lupus erythematosus disease activity index (SLEDAI). For the determination of levels of cytokines IFN-γ, IL-12, and IL17A, commercial ELISA kits were used. Genotyping of STAT4 rs7574865 (G > T) was performed by quantitative polymerase chain reaction (qPCR) using TaqMan probes. Results—The patients with SLE had a median age of 45 years with a range of disease duration from 4 years to 18 years; 45.6% were identified as having disease activity. In this sample, we identified a high IFN-γ prevalence of 35.4%. The levels of IFN-γ were higher in the patients with genotype TT than GG. We found that TT genotype conferred a higher risk of high IFN-γ when compared to the GG and GT genotypes. Conclusions—In this study, we identified that the polymorphic genotype TT of the STAT4 gene rs7574865 polymorphism is associated with increased levels of IFN-γ. However, its strength of association was weak, so complementary studies are needed to evaluate its impact on SLE patients. |
format | Online Article Text |
id | pubmed-10048585 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-100485852023-03-29 Association of the STAT4 Gene rs7574865 Polymorphism with IFN-γ Levels in Patients with Systemic Lupus Erythematosus Esparza Guerrero, Yussef Vazquez Villegas, Maria Luisa Nava Valdivia, Cesar Arturo Ponce Guarneros, Juan Manuel Perez Guerrero, Edsaul Emilio Gomez Ramirez, Eli Efrain Ramirez Villafaña, Melissa Contreras Haro, Betsabe Martinez Hernandez, Alejandra Cardona Muñoz, Ernesto German Nuño Arana, Ismael Gallardo Moya, Sergio Gabriel Celis, Alfredo Gonzalez Lopez, Laura Gamez Nava, Jorge Ivan Saldaña Cruz, Ana Miriam Genes (Basel) Article STAT4 plays an important role in disease activity in SLE patients. STAT4 particles have the capacity to activate the transcription of genes associated with the production of TH1 and Th17 lymphocytes, with a greater predominance on the production of IFN-γ and IL-17A. The presence of variants in STAT4 genes has a major impact on the generation of autoimmunity. However, there are few studies evaluating the impact of these variants on the production of proinflammatory cytokines such as IFN-γ and IL-17A. Methods—A case–control study was carried out with 206 Mexican mestizo patients residing in Western Mexico with a diagnosis of SLE and a group of 80 patients without autoimmune diseases was captured to determine the cut-off point for high IFN-γ levels. In this study, SLE patients with high IFN-γ levels were considered as cases (cut-off > 15.6 pg/mL), and SLE patients with normal IFN-γ levels were considered as controls (cut-off ≤ 15.6 pg/mL). Disease activity was identified from the systemic lupus erythematosus disease activity index (SLEDAI). For the determination of levels of cytokines IFN-γ, IL-12, and IL17A, commercial ELISA kits were used. Genotyping of STAT4 rs7574865 (G > T) was performed by quantitative polymerase chain reaction (qPCR) using TaqMan probes. Results—The patients with SLE had a median age of 45 years with a range of disease duration from 4 years to 18 years; 45.6% were identified as having disease activity. In this sample, we identified a high IFN-γ prevalence of 35.4%. The levels of IFN-γ were higher in the patients with genotype TT than GG. We found that TT genotype conferred a higher risk of high IFN-γ when compared to the GG and GT genotypes. Conclusions—In this study, we identified that the polymorphic genotype TT of the STAT4 gene rs7574865 polymorphism is associated with increased levels of IFN-γ. However, its strength of association was weak, so complementary studies are needed to evaluate its impact on SLE patients. MDPI 2023-02-21 /pmc/articles/PMC10048585/ /pubmed/36980810 http://dx.doi.org/10.3390/genes14030537 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Esparza Guerrero, Yussef Vazquez Villegas, Maria Luisa Nava Valdivia, Cesar Arturo Ponce Guarneros, Juan Manuel Perez Guerrero, Edsaul Emilio Gomez Ramirez, Eli Efrain Ramirez Villafaña, Melissa Contreras Haro, Betsabe Martinez Hernandez, Alejandra Cardona Muñoz, Ernesto German Nuño Arana, Ismael Gallardo Moya, Sergio Gabriel Celis, Alfredo Gonzalez Lopez, Laura Gamez Nava, Jorge Ivan Saldaña Cruz, Ana Miriam Association of the STAT4 Gene rs7574865 Polymorphism with IFN-γ Levels in Patients with Systemic Lupus Erythematosus |
title | Association of the STAT4 Gene rs7574865 Polymorphism with IFN-γ Levels in Patients with Systemic Lupus Erythematosus |
title_full | Association of the STAT4 Gene rs7574865 Polymorphism with IFN-γ Levels in Patients with Systemic Lupus Erythematosus |
title_fullStr | Association of the STAT4 Gene rs7574865 Polymorphism with IFN-γ Levels in Patients with Systemic Lupus Erythematosus |
title_full_unstemmed | Association of the STAT4 Gene rs7574865 Polymorphism with IFN-γ Levels in Patients with Systemic Lupus Erythematosus |
title_short | Association of the STAT4 Gene rs7574865 Polymorphism with IFN-γ Levels in Patients with Systemic Lupus Erythematosus |
title_sort | association of the stat4 gene rs7574865 polymorphism with ifn-γ levels in patients with systemic lupus erythematosus |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10048585/ https://www.ncbi.nlm.nih.gov/pubmed/36980810 http://dx.doi.org/10.3390/genes14030537 |
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