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  

作　　者：Fabiola Rabelo Jose Tadeu Stefano Ana Mercedes Cavaleiro Rodrigo Vieira Costa Lima Daniel Ferraz de Campos Mazo Flair Jose Carrilho Maria Lúcia Correa-Giannellac Claudia P.Oliveiraa 

机构地区：[1]Departamento de Gastroenterologia,Faculdade de Medicina FMUSP,Universidade de Sao Paulo,Sao Paulo,SP,Brazil [2]Hospital das Clinicas HCFMUSP,Departamento de Gastroenterologia,LIM07,Faculdade de Medicina,Universidade de Sao Paulo,Sao Paulo,SP,Brazil [3]Laboratório de Carboidratos e Radioimunensaio,LIM18,Hospital das Clinicas HCFMUSP(LIM07)Faculdade de Medicina,Universidade de Sao Paulo,Sao Paulo,Brazil [4]Programa de Pos-Graduacao em Medicina,Universidade Nove de Julho(UNINOVE),Sao Paulo,Brazil

出　　处：《Hepatobiliary & Pancreatic Diseases International》2018年第4期330-335,共6页国际肝胆胰疾病杂志（英文版）

基　　金：supported by the grant from Coordenacao de Aperfeicoamento de Pessoal de Nível Superior(CAPES)Grant no.Convênio PROAP 190/2014

摘　　要：Background: 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 p22 phox(CYBA) in NAFLD.Methods: 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.Results: 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/m2,P < 0.01). In addition, serum glucose and insulin levels increased significantly in the presence of NASH.Conclusions: There 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.Background: 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 p22 phox(CYBA) in NAFLD.Methods: 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.Results: 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/m2,P < 0.01). In addition, serum glucose and insulin levels increased significantly in the presence of NASH.Conclusions: There 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.

关 键 词：Non-alcoholic fatty liver disease Nonalcoholic steatohepatitis Genetic polymorphism Metabolic syndrome 

分 类 号：R[医药卫生]