Steatosis,
or accumulation of fat in liver cells, is a growing concern as an increasing proportion
of the population develops obesity and metabolic syndrome.
Steatosis
is common among people with chronic hepatitis C
-- and is associated with poorer response to interferon-based
therapy -- but research has shown that the process of fat accumulation appears
to differ in people with HCV genotype
3 compared with other genotypes.
"In
HCV
genotype 3-infected patients, the etiology of steatosis
appears to be closely correlated with unknown viral factors that increase intracellular
lipid levels," investigators from Duke University wrote in the January 15,
2008 Journal of Infectious Diseases. "We hypothesize that specific
sequence polymorphisms in HCV genotype 3 core protein may be associated with hepatic
intracellular lipid accumulation."
The investigators analyzed selected
serum samples from 8 HCV
genotype 3 patients with or without steatosis, sequencing the HCV core gene
to identify candidate polymorphisms (variations at a specific site on the genome)
associated with increased intracellular lipid levels.
Results
•
2
polymorphisms, at positions 182 and 186 of the core protein, correlated with the
presence (P = 0.03) and absence (P = 0.005) of hepatic steatosis.
•
Transfected
liver cell lines expressing core proteins with the steatosis-associated polymorphisms
had increased intracellular lipid levels compared with non-steatosis-associated
core isolates (P = 0.02).
•
Site-specific
mutations induced at positions 182 and 186 in steatosis-associated core genes
yielded proteins that had decreased intracellular lipid levels in transfected
cells (P = 0.03).
Conclusion
In
conclusion, the authors wrote, "We have identified polymorphisms in HCV core
protein genotype 3 that produce increased intracellular lipid levels and thus
may play a significant role in lipid metabolism or trafficking, contributing to
steatosis."
02/26/08
Reference
R Jhaveri, J McHutchison,
K Patel, and others. Specific polymorphisms in hepatitis C virus genotype 3 core
protein associated with intracellular lipid accumulation. Journal of Infectious
Diseases 197(2): 283-291. January 15, 2008.
