Association of polymorphisms of glutamate-cystein ligase and microsomal triglyceride transfer protein genes in non-alcoholic fatty liver disease.
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.
Oliveira
Claudia Pinto Marques Souza
CP
Department of Gastroenterology, University of Sao Paulo School of Medicine, Brazil. cpm@usp.br
Stefano
José Tadeu
JT
Cavaleiro
Ana Mercedes
AM
Zanella Fortes
Maria Angela Henriques
MA
Vieira
Suzana Maria
SM
Rodrigues Lima
Vicência Mara
VM
Santos
Telma Eugenio
TE
Santos
Virginia Nascimento
VN
de Azevedo Salgado
Ana Lucia Farias
AL
Parise
Edson Roberto
ER
Ferreira Alves
Venâncio Avancini
VA
Carrilho
Flair José
FJ
Corrêa-Giannella
Maria Lucia
ML
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
D002352:Carrier Proteins; C106092:microsomal triglyceride transfer protein; D005721:Glutamate-Cysteine Ligase