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

作者：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; Farias de Azevedo Salgado Ana Lucia; Parise Edson Roberto; Ferreira Alves Venancio Avancini; Carrilho Flair Jose; Correa Giannella Maria Lucia

来源：Journal of Gastroenterology and Hepatology, 2010, 25(2): 357-361.

DOI：10.1111/j.1440-1746.2009.06001.x

• fatty liver
• genetic susceptibility
• genetic polymorphisms
• microsomal TG transfer protein
• lipid metabolism
• glutamate-cystein ligase
• glutathione
• oxidative stress

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.

• 出版日期2010-2