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 genes...

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Published in:	Genes 2023-02, Vol.14 (3), p.537
Main Authors:	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
Format:	Article
Language:	eng
Subjects:	Alleles Autoimmune diseases Autoimmune Diseases - genetics Autoimmune Diseases - metabolism Autoimmunity Case-Control Studies Child, Preschool Cytokines Cytokines - genetics Disease Gene polymorphism Genes Genetic Predisposition to Disease Genotyping Helper cells Humans IFN-gamma Inflammation Interferon Interferon-gamma - genetics Interleukin 12 Interleukin-17 - genetics Laboratories Lupus Lupus Erythematosus, Systemic - genetics Lupus Erythematosus, Systemic - metabolism Lymphocytes Lymphocytes T Medical research Phosphorylation Polymerase chain reaction Polymorphism Polymorphism, Single Nucleotide Proteins STAT4 Stat4 protein STAT4 Transcription Factor - genetics Systemic lupus erythematosus γ-Interferon
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Summary:	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 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 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.
ISSN:	2073-4425 2073-4425