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Association of polymorphisms of glutamate-cystein ligase and microsomal triglyceride transfer protein genes in non-alcoholic fatty liver disease

Authors

  • Claudia Pinto Marques Souza Oliveira,

    Corresponding author
    1. Departments of Gastroenterology University of Sao Paulo School of Medicine, Brazil and
      Associate Professor Claudia PMS Oliveira, Department of Gastroenterology, University of Sao Paulo School of Medicine, Av. Dr. Enéas de Carvalho Aguiar n° 255, Instituto Central, # 9159, 05403-000, Sao Paulo, Brazil. Email: cpm@usp.br
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  • José Tadeu Stefano,

    1. Departments of Gastroenterology University of Sao Paulo School of Medicine, Brazil and
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  • Ana Mercedes Cavaleiro,

    1. Laboratory for Cellular and Molecular Endocrinology, Division of Endocrinology, University of Sao Paulo School of Medicine, Brazil and
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  • Maria Angela Henriques Zanella Fortes,

    1. Laboratory for Cellular and Molecular Endocrinology, Division of Endocrinology, University of Sao Paulo School of Medicine, Brazil and
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  • Suzana Maria Vieira,

    1. Laboratory for Cellular and Molecular Endocrinology, Division of Endocrinology, University of Sao Paulo School of Medicine, Brazil and
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  • Vicência Mara Rodrigues Lima,

    1. Departments of Gastroenterology University of Sao Paulo School of Medicine, Brazil and
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  • Telma Eugenio Santos,

    1. Departments of Gastroenterology University of Sao Paulo School of Medicine, Brazil and
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  • Virginia Nascimento Santos,

    1. Department of Gastroenterology, Federal University of Sao Paulo, Sao Paulo City, Sao Paulo, Brazil
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  • Ana Lucia Farias De Azevedo Salgado,

    1. Department of Gastroenterology, Federal University of Sao Paulo, Sao Paulo City, Sao Paulo, Brazil
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  • Édson Roberto Parise,

    1. Department of Gastroenterology, Federal University of Sao Paulo, Sao Paulo City, Sao Paulo, Brazil
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  • Venâncio Avancini Ferreira Alves,

    1. Departments of Pathology, University of Sao Paulo School of Medicine, Brazil
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  • Flair José Carrilho,

    1. Departments of Gastroenterology University of Sao Paulo School of Medicine, Brazil and
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  • Maria Lucia Corrêa-Giannella

    1. Laboratory for Cellular and Molecular Endocrinology, Division of Endocrinology, University of Sao Paulo School of Medicine, Brazil and
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Associate Professor Claudia PMS Oliveira, Department of Gastroenterology, University of Sao Paulo School of Medicine, Av. Dr. Enéas de Carvalho Aguiar n° 255, Instituto Central, # 9159, 05403-000, Sao Paulo, Brazil. Email: cpm@usp.br

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.

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