Association of a variant in the regulatory region of NADPH oxidase 4 gene and metabolic syndrome in patients with chronic hepatitis C.

Autor: Siqueira ER; 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., Pereira LB; 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., Stefano JT; 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., Patente T; 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., Cavaleiro AM; 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., Silva Vasconcelos LR; Liver Institute of Pernambuco, Arnóbio Marques Street, 282, Recife, Pernambuco, Brazil. luydson@yahoo.com.br., Carmo RF; College of Pharmaceutical Sciences, Federal University of São Francisco Valley, Avenida José de Sá Maniçoba - Centro, Petrolina, PE, Brazil. carmorodrigo@gmail.com., Moreira Beltrao Pereira LM; 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., Carrilho FJ; 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., Corrêa-Giannella ML; 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., Oliveira CP; 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.
Jazyk: angličtina
Zdroj: European journal of medical research [Eur J Med Res] 2015 Mar 28; Vol. 20, pp. 45. Date of Electronic Publication: 2015 Mar 28.
DOI: 10.1186/s40001-015-0136-2
Abstrakt: 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.
Databáze: MEDLINE
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