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

Abstract

Backgrounds: Neural growth factor (NGF) is a neurotrophin that can interact with the p75 NTR receptor and initiate a cascade of reactions that determines cell survival or death, and both are associated with the physiology of liver tissue. Single nucleotide polymorphisms (SNPs) in the NGF and p75 NTR genes have been investigated in different pathologies; however, there are no studies that have analyzed their biological roles in the hepatic microenvironment. In the present study, we evaluated the impact of SNPs in these genes on the maintenance of liver function at different stages of inflammation and fibrosis in patients with chronic viral liver disease in the Brazilian Amazon. Methods: The SNPs-198C > T, Arg80Gln, Val72Met, Ala35Val, Ala18Ala and Ser205Leu were genotyped by real-time PCR in samples from patients with chronic viral hepatitis stratified by stage of inflammation and liver fibrosis. Histopathological, viral load (VL), liver enzyme and comorbidities data were obtained from updated medical records. Other aspects were highlighted by applied epidemiological questionnaires. Results: The-198C/T and Ala35Val polymorphisms in NGF were associated with changes in histopathological profiles, VL and liver enzymes. Ser205Leu polymorphism in p75 NTR was associated only with changes in VL and liver enzymes. Polymorphic frequencies were variable among different ethnic populations, mainly for biologically relevant polymorphisms. A multifactorial network of interactions has been established based on genetic, virological, behavioral and biochemical aspects. Conclusion: Mutations in the NGF (−198C > T, Ala35Val) and p75 NTR (Ser205Leu) genes, within the list of multifactorial aspects, are associated with liver function in different histopathological profiles of patients with chronic viral liver disease in the Brazilian Amazon.

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

“…The transaminase ratio was stable between genotypes and sexes, indicative of chronic infection, but not relevant for estimating the stage of fibrosis [13]. Recent studies by our group show that in liver fibrosis, viral load, in fact, is more associated with the histological profile than liver integrity enzymes [14].…”

“…In the multiple logistic regression, the allele T was also associated with advanced fibrosis; however, the decrease in the statistical probability is indicative of other factors influencing liver histopathology. In recent publications, we discard alcoholism as a behavioral factor associated with liver fibrosis [14].…”

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

“…The transaminase ratio was stable between genotypes and sexes, indicative of chronic infection, but not relevant for estimating the stage of brosis (13). Recent studies by our group show that in liver brosis, viral load, in fact, is more associated with the histological pro le than liver integrity enzymes (14).…”

“…In the multiple logistic regression, the allele T was also associated with advanced brosis; however, the decrease in the statistical probability is indicative of other factors in uencing liver histopathology. In recent publications, we discard alcoholism as a behavioral factor associated with liver brosis (14).…”

Sex and Foxp3 -924a/g Gene Polymorphism May Be Associated With the Clinical and Pathological Aspects of Chronic Viral Diseases

“…In the multivariate analysis, the allele A was also associated with advanced brosis; however, the decrease in the statistical probability is indicative of other factors in uencing liver histopathology. In recent publications, we discard alcoholism as a behavioral factor associated with liver brosis (14).…”