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- Posted Tuesday September 1, 2015
TGen identifies potential genes associated with the most common form of liver damage
First-of-its-kind exploratory study shows source of liver damage could be traced by analyzing microRNA
PHOENIX, Ariz. - Sept. 1, 2015 - In a
first-of-its-kind exploratory study, the Translational
Genomics Research Institute (TGen) has identified a potential
gene associated with the initiation of the most common cause of
liver damage.
Nonalcoholic fatty liver disease (NAFLD) is the most common cause
of liver damage. In this study, published in the September edition
of Translational Research, TGen scientists sequenced
microRNAs (miRNAs) from liver biopsies, spelling out their
biochemical molecules to identify several potential gene targets
associated with NAFLD-related liver damage.
The miRNAs - RNA molecules that regulate gene expression - were
obtained from liver biopsies of 30 female candidates for gastric
bypass surgery: 15 with, and 15 without, NAFLD liver damage.
Using the most advanced technology to refine the data, researchers
identified several potential gene targets associated with
NAFLD-related liver damage. Specifically, they found that a
particular miRNA called miR-182 produced a strong association with
a protein called FOX03.
"Because of the known role of miR-182 in mechanisms related to
liver cancer, we sought to investigate this miRNA in NAFLD-related
liver damage by looking at relevant target genes," said TGen
Research Associate Fatjon Leti, the study's lead author. "We found
that levels of FOX03, which has been implicated in liver
metabolism, to be significantly decreased."
Importantly, researchers observed a significant suppression of
FOX03 protein levels in damaged livers, compared to those without
liver damage, suggesting a potential role for this gene in the
initiation of liver disease.
"These finding support a role for liver miRNAs in the disease
development of NAFLD-related damage, and yield possible new insight
into the molecular mechanisms underlying the initiation and
progression of liver damage and eventual liver failure," said Dr.
Johanna DiStefano, Professor and Director of TGen's Diabetes,
Cardiovascular & Metabolic Diseases Division, and the study's
senior author.
"To our knowledge, this is the first study to apply a
high-throughput sequencing approach to the investigation of liver
miRNAs in NAFLD-related liver damage," DiStefano said.
The authors cite limitations in this particular study: The study's
small sample, and the fact that all 30 patients were obese females
who were candidates for gastric bypass surgery, which may have
limited the data. They were selected because obesity is a
significant risk factor for NAFLD outcomes, and because of the
value of obtaining unbiased liver samples.
"We consider this study an exploratory one, and we acknowledge
that validation in a larger, independent dataset will be necessary
to confirm our findings," DiStefano said. "The results reported
here do not allow us to make specific conclusions about miRNAs and
biological pathways. Additional studies will be necessary to
confirm the role of specific miRNAs in liver damage."
Also contributing to this study - High-throughput sequencing
reveals altered expression of hepatic microRNAs in nonalcoholic
fatty liver disease-related fibrosis - were the Geisinger
Obesity Institute, and Temple University School of Medicine.
This study was supported by TGen, and by the National Institutes
of Health (NIH) through grant DK091601.
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About TGen
Translational Genomics Research Institute (TGen) is a Phoenix,
Arizona-based non-profit organization dedicated to conducting
groundbreaking research with life changing results. TGen is focused
on helping patients with cancer, neurological disorders and
diabetes, through cutting edge translational research (the process
of rapidly moving research towards patient benefit). TGen
physicians and scientists work to unravel the genetic components of
both common and rare complex diseases in adults and children.
Working with collaborators in the scientific and medical
communities literally worldwide, TGen makes a substantial
contribution to help our patients through efficiency and
effectiveness of the translational process. For more information,
visit:www.tgen.org.
Press Contact:
Steve Yozwiak
TGen Senior Science Writer
602-343-8704
[email protected]
