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Title: Association of polymorphisms of glutamate-cystein ligase and microsomal triglyceride transfer protein genes in non-alcoholic fatty liver disease
Authors: Marques Souza Oliveira, Claudia Pinto
Stefano, Jose Tadeu
Cavaleiro, Ana Mercedes
Henriques Zanella Fortes, Maria Angela
Vieira, Suzana Maria
Rodrigues Lima, Vicencia Mara
Santos, Telma Eugenio
Santos, Virginia Nascimento [UNIFESP]
Farias de Azevedo Salgado, Ana Lucia [UNIFESP]
Parise, Edson Roberto [UNIFESP]
Ferreira Alves, Venancio Avancini
Carrilho, Flair Jose
Correa-Giannella, Maria Lucia
Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Keywords: fatty liver
genetic susceptibility
genetic polymorphisms
microsomal TG transfer protein
lipid metabolism
glutamate-cystein ligase
oxidative stress
Issue Date: 1-Feb-2010
Publisher: Wiley-Blackwell
Citation: Journal of Gastroenterology and Hepatology. Malden: Wiley-Blackwell Publishing, Inc, v. 25, n. 2, p. 357-361, 2010.
Abstract: Background and Aims: Although the metabolic risk factors for non-alcoholic fatty liver disease (NAFLD) progression have been recognized, the role of genetic susceptibility remains a field to be explored. the aim of this study was to examine the frequency of two polymorphisms in Brazilian patients with biopsy-proven simple steatosis or non-alcoholic steatohepatitis (NASH): -493 G/T in the MTP gene, which codes the protein responsible for transferring triglycerides to nascent apolipoprotein B, and -129 C/T in the GCLC gene, which codes the catalytic subunit of glutamate-cystein ligase in the formation of glutathione.Methods: One hundred and thirty-one biopsy-proven NAFLD patients (n = 45, simple steatosis; n = 86, NASH) and 141 unrelated healthy volunteers were evaluated. Genomic DNA was extracted from peripheral blood cells, and the -129 C/T polymorphism of the GCLC gene was determined by restriction fragment length polymorphism (RFLP). the -493 G/T polymorphism of the MTP gene was determined by direct sequencing of the polymerase chain reaction products.Results: the presence of at least one T allele in the -129 C/T polymorphism of the GCLC gene was independently associated with NASH (odds ratio 12.14, 95% confidence interval 2.01-73.35; P = 0.007), whereas, the presence of at least one G allele in the -493 G/T polymorphism of the MTP gene differed slightly between biopsy-proven NASH and simple steatosis.Conclusion: This difference clearly warrants further investigation in larger samples. These two polymorphisms could represent an additional factor for consideration in evaluating the risk of NAFLD progression. Further studies involving a larger population are necessary to confirm this notion.
ISSN: 0815-9319
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