title: Association of polymorphisms of glutamate-cystein ligase and microsomal triglyceride transfer protein genes in non-alcoholic fatty liver disease.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Gastroenterology, University of Sao Paulo School of Medicine, Brazil. cpm@usp.br
authors.forename: Claudia Pinto Marques Souza
authors.initials: CP
authors.lastname: Oliveira
authors.forename: José Tadeu
authors.initials: JT
authors.lastname: Stefano
authors.forename: Ana Mercedes
authors.initials: AM
authors.lastname: Cavaleiro
authors.forename: Maria Angela Henriques
authors.initials: MA
authors.lastname: Zanella Fortes
authors.forename: Suzana Maria
authors.initials: SM
authors.lastname: Vieira
authors.forename: Vicência Mara
authors.initials: VM
authors.lastname: Rodrigues Lima
authors.forename: Telma Eugenio
authors.initials: TE
authors.lastname: Santos
authors.forename: Virginia Nascimento
authors.initials: VN
authors.lastname: Santos
authors.forename: Ana Lucia Farias
authors.initials: AL
authors.lastname: de Azevedo Salgado
authors.forename: Edson Roberto
authors.initials: ER
authors.lastname: Parise
authors.forename: Venâncio Avancini
authors.initials: VA
authors.lastname: Ferreira Alves
authors.forename: Flair José
authors.initials: FJ
authors.lastname: Carrilho
authors.forename: Maria Lucia
authors.initials: ML
authors.lastname: Corrêa-Giannella
mesh_terms: D001706:Biopsy; D001938:Brazil; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005234:Fatty Liver / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005721:Glutamate-Cysteine Ligase / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D002352:Carrier Proteins; C106092:microsomal triglyceride transfer protein; D005721:Glutamate-Cysteine Ligase