title: Association of a variant in the regulatory region of NADPH oxidase 4 gene and metabolic syndrome in patients with chronic hepatitis C.
abstract: BACKGROUND
  Given the important contribution of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system to the generation of reactive oxygen species induced by hepatitis C virus (HCV), we investigated two single nucleotide polymorphisms (SNPs) in the putative regulatory region of the genes encoding NADPH oxidase 4 catalytic subunit (NOX4) and its regulatory subunit p22phox (CYBA) and their relation with metabolic and histological variables in patients with HCV.
  
  
  METHODS
  One hundred seventy eight naïve HCV patients (49.3% male; 65% HCV genotype 1) with positive HCV RNA were genotyped using specific primers and fluorescent-labeled probes for SNPs rs3017887 in NOX4 and -675 T → A in CYBA.
  
  
  RESULTS
  No association was found between the genotype frequencies of NOX4 and CYBA SNPs and inflammation scores or fibrosis stages in the overall population. The presence of the CA + AA genotypes of the NOX4 SNP was nominally associated with a lower alanine aminotransferase (ALT) concentration in the male population (CA + AA = 72.23 ± 6.34 U/L versus CC = 100.22 ± 9.85; mean ± SEM; P = 0.05). The TT genotype of the CYBA SNP was also nominally associated with a lower ALT concentration in the male population (TT = 84.01 ± 6.77 U/L versus TA + AA = 109.67 ± 18.37 U/L; mean ± SEM; P = 0.047). The minor A-allele of the NOX4 SNP was inversely associated with the frequency of metabolic syndrome (MS) in the male population (odds ratio (OR): 0.15; 95% confidence interval (CI): 0.03 to 0.79; P = 0.025).
  
  
  CONCLUSIONS
  The results suggest that the evaluated NOX4 and CYBA SNPs are not direct genetic determinants of fibrosis in HCV patients, but nevertheless NOX4 rs3017887 SNP could indirectly influence fibrosis susceptibility due to its inverse association with MS in male patients.
authors.affiliation: Department of Gastroenterology (LIM-07), School of Medicine, University of São Paulo, Av. Dr Arnaldo, 455, 3° Andar, #3115, Cep.: 1246903, São Paulo, Brazil. erikarfs@gmail.com.|Department of Gastroenterology, School of Medicine, University of Pernambuco, Av. Professor Morais Rego, 1235, Pernambuco, Brazil. erikarfs@gmail.com.|Liver Institute of Pernambuco, Arnóbio Marques Street, 282, Recife, Pernambuco, Brazil. erikarfs@gmail.com.
authors.forename: Erika Rabelo Forte de
authors.initials: ER
authors.lastname: Siqueira
authors.affiliation: Department of Gastroenterology (LIM-07), School of Medicine, University of São Paulo, Av. Dr Arnaldo, 455, 3° Andar, #3115, Cep.: 1246903, São Paulo, Brazil. lpereiras@hotmail.com.|Department of Gastroenterology, School of Medicine, University of Pernambuco, Av. Professor Morais Rego, 1235, Pernambuco, Brazil. lpereiras@hotmail.com.|Liver Institute of Pernambuco, Arnóbio Marques Street, 282, Recife, Pernambuco, Brazil. lpereiras@hotmail.com.
authors.forename: Luciano Beltrao
authors.initials: LB
authors.lastname: Pereira
authors.affiliation: Department of Gastroenterology (LIM-07), School of Medicine, University of São Paulo, Av. Dr Arnaldo, 455, 3° Andar, #3115, Cep.: 1246903, São Paulo, Brazil. jstefano@usp.br.
authors.forename: Jose Tadeu
authors.initials: JT
authors.lastname: Stefano
authors.affiliation: Laboratory for Cellular and Molecular Endocrinology - LIM-25, School of Medicine, University of São Paulo, Av. Dr Arnaldo, 455, 3° Andar, #3115, São Paulo, SP, Brazil. thiago.patente@usp.br.
authors.forename: Thiago
authors.initials: T
authors.lastname: Patente
authors.affiliation: Laboratory for Cellular and Molecular Endocrinology - LIM-25, School of Medicine, University of São Paulo, Av. Dr Arnaldo, 455, 3° Andar, #3115, São Paulo, SP, Brazil. cavana@lim25.fm.usp.br.
authors.forename: Ana Mercedes
authors.initials: AM
authors.lastname: Cavaleiro
authors.affiliation: Liver Institute of Pernambuco, Arnóbio Marques Street, 282, Recife, Pernambuco, Brazil. luydson@yahoo.com.br.
authors.forename: Luydson Richardson
authors.initials: LR
authors.lastname: Silva Vasconcelos
authors.affiliation: College of Pharmaceutical Sciences, Federal University of São Francisco Valley, Avenida José de Sá Maniçoba - Centro, Petrolina, PE, Brazil. carmorodrigo@gmail.com.
authors.forename: Rodrigo Feliciano
authors.initials: RF
authors.lastname: Carmo
authors.affiliation: Department of Gastroenterology, School of Medicine, University of Pernambuco, Av. Professor Morais Rego, 1235, Pernambuco, Brazil. leilapereira@pq.cnpq.br.|Liver Institute of Pernambuco, Arnóbio Marques Street, 282, Recife, Pernambuco, Brazil. leilapereira@pq.cnpq.br.
authors.forename: Leila Maria
authors.initials: LM
authors.lastname: Moreira Beltrao Pereira
authors.affiliation: Department of Gastroenterology (LIM-07), School of Medicine, University of São Paulo, Av. Dr Arnaldo, 455, 3° Andar, #3115, Cep.: 1246903, São Paulo, Brazil. fjcarril@usp.br.
authors.forename: Flair Jose
authors.initials: FJ
authors.lastname: Carrilho
authors.affiliation: Laboratory for Cellular and Molecular Endocrinology - LIM-25, School of Medicine, University of São Paulo, Av. Dr Arnaldo, 455, 3° Andar, #3115, São Paulo, SP, Brazil. malugia@lim25.fm.usp.br.|NUCEL-NETCEM Cell and Molecular Therapy Center, School of Medicine, University of São Paulo, Av. Dr Arnaldo, 455, 3° Andar, #3115, São Paulo, SP, Brazil. malugia@lim25.fm.usp.br.
authors.forename: Maria Lucia
authors.initials: ML
authors.lastname: Corrêa-Giannella
authors.affiliation: Department of Gastroenterology (LIM-07), School of Medicine, University of São Paulo, Av. Dr Arnaldo, 455, 3° Andar, #3115, Cep.: 1246903, São Paulo, Brazil. cpm@usp.br.
authors.forename: Claudia P
authors.initials: CP
authors.lastname: Oliveira
mesh_terms: D019698:Hepatitis C, Chronic / Q000150:complications* / Q000235:genetics; D006801:Humans; D024821:Metabolic Syndrome / Q000235:genetics*; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498910:NOX4 protein, human; C086986:CYBA protein, human