a81570a3-5f41-4e21-9ae5-c0e11fbcc187
title
Polymorphisms of  microsomal triglyceride transfer protein  gene and  manganese superoxide dismutase  gene in non-alcoholic steatohepatitis.
b692a873-df36-4cf1-bb8c-b4d1f39b898a
abstract
BACKGROUND/AIMS: The pathogenesis of non-alcoholic steatohepatitis (NASH) is poorly understood. The aim of this study was to examine genetic influences on NASH pathogenesis. METHODS: Blood samples from 63 patients with biopsy-proven NASH and 150 healthy controls were analyzed by the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Two functional polymorphisms were studied: the  -493 G/T  polymorphism in the promoter of  microsomal triglyceride transfer protein  (MTP) and the  1183 T/C  polymorphism in the mitochondrial targeting sequence of  manganese superoxide dismutase  ( MnSOD ). RESULTS: NASH patients had a much higher incidence of the MTP gene G allele (P=0.001) and of the G/G genotype (P=0.002) compared to the controls. Fat occupied more area in liver lobules and the stage of NASH was advanced in patients with the G/G-genotype than in patients with G/T-genotype (P=0.04). NASH patients also had a higher incidence of the  MnSOD  T/T genotype (P=0.016). CONCLUSIONS: The G allele in the MTP promoter leads to decreased MTP transcription, less export of triglyceride from hepatocytes, and greater intracellular triglyceride accumulation. The T allele in  MnSOD  mitochondrial targeting sequence leads to less transport of  MnSOD  to the mitochondria. Therefore, functional polymorphisms in MTP and  MnSOD  may be involved in determining susceptibility of NASH.