Association between the CYBA and NOX4 genes of NADPH oxidase and its relationship with metabolic syndrome in non-alcoholic fatty liver disease in Brazilian population

Autor: Rodrigo Vieira Costa Lima, José Tadeu Stefano, Fabiola Rabelo, Daniel Ferraz de Campos Mazo, Claudia P. Oliveira, Maria Lúcia Corrêa-Giannella, Ana Mercedes Cavaleiro, Flair José Carrilho
Rok vydání: 2017
Předmět:
0301 basic medicine
Liver Cirrhosis
Male
0302 clinical medicine
Gene Frequency
Non-alcoholic Fatty Liver Disease
Risk Factors
Genotype
Medicine
Metabolic Syndrome
education.field_of_study
NADPH oxidase
biology
ESTRESSE OXIDATIVO
Fatty liver
Gastroenterology
NOX4
Middle Aged
Phenotype
NADPH Oxidase 4
030211 gastroenterology & hepatology
Female
Brazil
Adult
Genetic Markers
medicine.medical_specialty
Population
Single-nucleotide polymorphism
digestive system
Polymorphism
Single Nucleotide
03 medical and health sciences
Internal medicine
Humans
Genetic Predisposition to Disease
education
Genetic Association Studies
Aged
Hepatology
business.industry
nutritional and metabolic diseases
NADPH Oxidases
medicine.disease
digestive system diseases
030104 developmental biology
Endocrinology
Cross-Sectional Studies
biology.protein
P22phox
Metabolic syndrome
Insulin Resistance
business
Zdroj: Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual)
Universidade de São Paulo (USP)
instacron:USP
ISSN: 1499-3872
Popis: Oxidative stress has been implicated in the progression of severe forms of non-alcoholic fatty liver disease (NAFLD). NADPH oxidase produces reactive oxygen species. In the present study, we investigated for the first time two single nucleotide polymorphisms (SNPs) in the regulatory region of genes encoding NADPH oxidase 4 (NOX4) and p22phox (CYBA) in NAFLD.A total of 207 biopsy-proven NAFLD patients [simple steatosis (n = 27); nonalcoholic steatohepatitis (NASH) (n = 180)] were evaluated. Genomic DNA was extracted from peripheral blood cells, and polymorphisms in CYBA (unregistered) and NOX4 (rs3017887) were determined by direct sequencing of PCR.Associations of CYBA-675 T/A with high-density lipoprotein (HDL) (TT vs TA vs AA; P 0.01) and triglycerides (TGL) (TT vs XA; P 0.01) were observed only in NASH patients. For polymorphisms in the NOX4 gene, NOX4 (rs3017887) CA + AA genotypes was significant associated with alanine aminotransferase (ALT) (CA + AA vs CC; P = 0.02). However, there was no association of SNPs in the CYBA and NOX4 genes encoding the NADPH oxidase system proteins and the presence of NASH. Regarding the clinical results, it was observed that the most advanced degrees of fibrosis occurred in patients diagnosed with type 2 diabetes mellitus (66.9% vs 37.5%, P 0.01) and those who were more obese (32.2 vs 29.0 kg/mThere were associations between the presence of the allele A in the NOX4 SNP and a higher concentration of ALT in the NAFLD population; between the presence of the AA genotype in the polymorphism of the CYBA-675 T/A CYBA gene and a higher level of TGL and lower HDL in NASH patients. The presence of metabolic syndrome was associated with advanced degrees of fibrosis in NAFLD patients.
Databáze: OpenAIRE
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