The −3279C>A and −924A>G polymorphisms in the FOXP3 Gene Are Associated With Viral Load and Liver Enzyme Levels in Patients With Chronic Viral Liver Diseases

Abstract

The transcription factor FOXP3 is an essential marker of the development and activation of regulatory T cells (Tregs), which are cells specialized in the regulation and normal tolerance of the immune response. In the context of chronic viral liver diseases, Tregs participate in the maintenance of infections by promoting histopathological control and favor the immune escape of viral agents by suppressing the antiviral response. Single nucleotide polymorphisms (SNPs) may influence the function of FOXP3 in a number of pathological conditions. The present study sought to evaluate the influence of SNPs in the FOXP3 gene promoter region in patients with chronic viral liver diseases. Three SNPs (−3279C>A, −2383C>T, and −924A>G) were analyzed in groups of patients with chronic hepatitis C (CHC), active chronic hepatitis B (CHB-A), inactive chronic hepatitis B (CHB-I), and a healthy control group (CG) using real-time PCR. The frequencies of the polymorphic variants were compared between groups and correlated with liver histopathological characteristics and enzyme levels [i.e., alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase (GGT)] obtained via biopsy and from the clinical records of the participating patients, respectively. For the −2338C>T SNP, no significant differences were found in the frequencies of variants between groups or in the histological findings. Significant associations between the polymorphisms and the CHB-I group were not established. The −3279C>A SNP was associated with altered viral loads (log10) and GGT levels in CHC patients with advanced stages of inflammatory activity and liver fibrosis. The −924A>G SNP was associated with altered viral loads (log10) and liver enzyme levels among CHB-A patients with milder inflammation and fibrosis. However, the frequencies of the −3279C>A and −924A>G polymorphisms were not directly associated with the histopathological profiles of the analyzed patients. These polymorphic variants may influence hepatic function in patients with chronic viral liver diseases but are not directly associated with the establishment of the degree of inflammatory activity and liver fibrosis.

Sex and FOXP3 gene rs2232365 polymorphism may be associated with the clinical and pathological aspects of chronic viral diseases

“…It seems counterintuitive to associate an anti-in ammatory factor with the risk of tissue aggression; however, these ndings corroborate previous studies that suggest that variant T favors the persistence of viral infection in patients with brosis (10). With the increase in VL, there is a long-term pro-brogenic tendency induced by chronic in ammation and continuous response to healing (11), resulting in the uctuation of pre-cirrhotic biomarkers (12), such as GGT.…”

The Epidemiological Impact of STIs among General and Vulnerable Populations of the Amazon Region of Brazil: 30 years of Surveillance

“…Mutations in the FoxP3 gene, SNP-924 A > G, showed that G carrier status was associated with altered viral loads and liver enzyme levels in patients with chronic active hepatitis B (CHB-A) with inflammation and fibrosis. However, the frequencies of SNP-3279 C > A, A and-924 A > G, G were not directly associated with the histopathological profiles of the patients investigated [ 148 ]. It was also observed that the hepatic levels of mRNA expression of the NGF and p75NTR genes decreased and increased, respectively, in relation to the stage of inflammatory activity in HBV carriers.…”

NGF (−198C > T, Ala35Val) and p75NTR (Ser205Leu) gene mutations are associated with liver function in different histopathological profiles of the patients with chronic viral hepatitis in the Brazilian Amazon

“…Screening for inclusion was based on clinical and laboratory results as previously described (Pereira et al, 2018): Patients with persistent HBsAg for more than 6 months, positive or negative HBeAg, positive anti-HBeAg, and clinical and histological changes were included among patients with chronic hepatitis B (PCHB). Patients characterized by clinical and histological changes, variations in serum liver enzyme levels and positive viral load for Hepacivirus C were included in the group of patients with chronic hepatitis C (PCHC).…”

“…A control group (CG) of 300 blood donors from the Center for Hemotherapy and Hematology of Pará Foundation (HEMOPA), seronegative, and undetectable viral load for HBV, Hepacivirus C, and other agents typically screened in blood bank screening were determined. This group is specifically used to compare the genetic frequency of the studied polymorphisms (Pereira et al, 2018).…”