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

Imagem de Miniatura
Arquivos
art_RABELO_Association_between_the_CYBA_and_NOX4_genes_of_2018.PDF (414.95 KB)
Citações na Scopus
10
Tipo de produção
article
Data de publicação
2018
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
ELSEVIER SCIENCE BV
Autores
Citação
HEPATOBILIARY & PANCREATIC DISEASES INTERNATIONAL, v.17, n.4, p.330-335, 2018
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
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 p22phox (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/m(2), 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.
Palavras-chave
Non-alcoholic fatty liver disease, Nonalcoholic steatohepatitis, Genetic polymorphism, Metabolic syndrome
URI
https://observatorio.fm.usp.br/handle/OPI/29451
Referências
  1. American Diabetes Association, 2017, Diabetes Care, V40, pS11
  2. Bedard K, 2007, PHYSIOL REV, V87, P245, DOI 10.1152/physrev.00044.2005
  3. Bedard K, 2009, HUM MUTAT, V30, P1123, DOI 10.1002/humu.21029
  4. Bettaieb A, 2015, GASTROENTEROLOGY, V149, P468, DOI 10.1053/j.gastro.2015.04.009
  5. Brunt EM, 2009, CLIN LIVER DIS, V13, P533, DOI 10.1016/j.cld.2009.07.008
  6. Burt AD, 2015, SEMIN LIVER DIS, V35, P207, DOI 10.1055/s-0035-1562942
  7. Chalasani N, 2012, GASTROENTEROLOGY, V142, P1592, DOI 10.1053/j.gastro.2012.04.001
  8. Cohen DE, 2013, SEMIN LIVER DIS, V33, P380, DOI 10.1055/s-0033-1358519
  9. De Minicis S, 2010, HEPATOLOGY, V52, P1420, DOI 10.1002/hep.23804
  10. Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults, 2001, JAMA-J AM MED ASSOC, V285, P2486, DOI 10.1001/JAMA.285.19.2486
  11. de Siqueira ERF, 2015, EUR J MED RES, V20, DOI 10.1186/s40001-015-0136-2
  12. Hirschhorn JN, 2011, ANNU REV MED, V62, P11, DOI 10.1146/annurev.med.091708.162036
  13. Hodgkinson AD, 2003, DIABETES CARE, V26, P3111, DOI 10.2337/diacare.26.11.3111
  14. Jiang JX, 2012, FREE RADICAL BIO MED, V53, P289, DOI 10.1016/j.freeradbiomed.2012.05.007
  15. Jose GS, 2008, CLIN SCI, V114, P173, DOI 10.1042/CS20070130
  16. Kleiner DE, 2005, HEPATOLOGY, V41, P1313, DOI 10.1002/hep.20701
  17. Lan T, 2015, PLOS ONE, V10, DOI 10.1371/journal.pone.0129743
  18. Liang S, 2016, FRONT PHYSIOL, V7, DOI 10.3389/fphys.2016.00017
  19. Lim SC, 2009, DIABETOLOGIA, V52, P1343, DOI 10.1007/s00125-009-1368-x
  20. Makkonen J, 2009, J HEPATOL, V50, P1035, DOI 10.1016/j.jhep.2008.12.025
  21. Moreno MU, 2007, J HYPERTENS, V25, P1620, DOI 10.1097/HJH.0b013e3281ac211d
  22. Oliveira CP, 2015, CLIN RES HEPATOL GAS, V39, pS35, DOI 10.1016/j.clinre.2015.05.014
  23. Parker HM, 2012, J HEPATOL, V56, P944, DOI 10.1016/j.jhep.2011.08.018
  24. Patente TA, 2015, GENE, V568, P50, DOI 10.1016/j.gene.2015.05.017
  25. Quigley EM, 2015, SEMIN LIVER DIS, V35, P262, DOI 10.1055/s-0035-1562946
  26. Sancho P, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0045285
  27. Song HR, 2008, AM J CLIN NUTR, V88, P16
  28. Sookoian S, 2015, WORLD J GASTROENTERO, V21, P711, DOI 10.3748/wjg.v21.i3.711
  29. Tariq Z, 2014, LIVER INT, V34, pE180, DOI 10.1111/liv.12523
  30. Wang C, 2017, BIOMED REP, V7, P95, DOI 10.3892/br.2017.926
  31. Wu KT, 2016, J CLIN LIPIDOL, V10, P420, DOI 10.1016/j.jacl.2015.12.026
  32. Zegers D, 2016, CLIN RES HEPATOL GAS, V40, P715, DOI 10.1016/j.clinre.2016.05.004

Coleções
Artigos e Materiais de Revistas Científicas - FM/MGT
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - LIM/07
Artigos e Materiais de Revistas Científicas - LIM/18
Artigos e Materiais de Revistas Científicas - ODS/03