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

Leonn Mendes Soares Pereira; Ednelza da Silva Graça Amoras; Simone Regina Souza da Silva Conde; Sâmia Demachki; Eduardo José Melo Dos Santos; Sandra Souza Lima; Ricardo Ishak; Antonio Carlos Rosário Vallinoto

doi:10.1186/s10020-019-0134-x

NGF (-198C > T, Ala35Val) and p75^NTR (Ser205Leu) gene mutations are associated with liver function in different histopathological profiles of the patients with chronic viral hepatitis in the Brazilian Amazon

Mol Med. 2020 Jan 29;26(1):12. doi: 10.1186/s10020-019-0134-x.

Affiliations

¹ Virology Laboratory, Biological Science Institute, Federal University of Pará, Belém, Pará, Brazil.
² Postgraduate Program in Biology of Infectious and Parasitic Agents, Biological Science Institute, Federal University of Pará, Belém, Pará, Brazil.
³ School of Medicine, Health Science Institute, Federal University of Pará, Belém, Pará, Brazil.
⁴ Laboartory of Human and Medical Genetics, Biological Science Institute, Federal University of Pará, Belém, Pará, Brazil.
⁵ Virology Laboratory, Biological Science Institute, Federal University of Pará, Belém, Pará, Brazil. vallinoto@ufpa.com.
⁶ Postgraduate Program in Biology of Infectious and Parasitic Agents, Biological Science Institute, Federal University of Pará, Belém, Pará, Brazil. vallinoto@ufpa.com.

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.

Keywords: Brazilian Amazon; Hepatic physiopathology; Liver diseases; Neurotrophins; Polymorphisms.

MeSH terms

Amino Acid Substitution*
Cross-Sectional Studies
Female
Hepatitis, Viral, Human / genetics
Hepatitis, Viral, Human / physiopathology*
Hepatitis, Viral, Human / virology
Humans
Liver Function Tests
Male
Nerve Growth Factor / genetics*
Nerve Tissue Proteins / genetics*
Polymorphism, Single Nucleotide
Receptors, Nerve Growth Factor / genetics*
Viral Load

Substances

NGF protein, human
NGFR protein, human
Nerve Tissue Proteins
Receptors, Nerve Growth Factor
Nerve Growth Factor