Polymorphisms of microsomal triglyceride transfer protein gene and manganese superoxide dismutase gene in non-alcoholic steatohepatitis.
OBJECTIVE
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.
Namikawa
Chikako
C
Department of Gastroenterology and Hepatology, Kochi Medical School, Nankoku 783-8505 Japan.
Shu-Ping
Zhang
Z
Vyselaar
John Raynor
JR
Nozaki
Yasuko
Y
Nemoto
Yoshihisa
Y
Ono
Masafumi
M
Akisawa
Naoaki
N
Saibara
Toshiji
T
Hiroi
Makoto
M
Enzan
Hideaki
H
Onishi
Saburo
S
D000328:Adult; D000447:Aldehydes / Q000378:metabolism; D000483:Alleles; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics; D005234:Fatty Liver / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D006521:Hepatitis, Chronic / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D013482:Superoxide Dismutase / Q000235:genetics*; D013577:Syndrome
D000447:Aldehydes; D002352:Carrier Proteins; C106092:microsomal triglyceride transfer protein; D004247:DNA; D013482:Superoxide Dismutase; C027576:4-hydroxy-2-nonenal