Hepatic gene expression in patients with obesity‐related non‐alcoholic steatohepatitis

Younossi, Zobair M.; Gorreta, Francesco; Ong, Janus P.; Schlauch, Karen; Giacco, Luca Del; Elariny, Hazem; Meter, Amy Van; Younoszai, Abraham; Goodman, Zachary; Baranova, Ancha; Christensen, Alan C.; Grant, Geraldine M.; Chandhoke, Vikas

doi:10.1111/j.1478-3231.2005.01117.x

Cited by 106 publications

(120 citation statements)

References 63 publications

Supporting

Mentioning

108

Contrasting

Unclassified

Order By: Relevance

“…These genes encode versican (CPSG2), matrix metalloproteinase 2/gelatinase A (MMP2), and vascular endothe- lial growth factor D (FIGF). 31 Furthermore, the expression of survival factor ARL6IP/RAMER was also decreased in NASH, suggesting a shift in cellular homeostasis toward apoptosis via an increase in caspase 9 activity. 39 These results also indicate that the FGFR2 gene encoding fibroblast growth factor receptor 2 is significantly upregulated at earlier stages of NAFLD.…”

Section: Discussionmentioning

confidence: 99%

“…30 A per-chip background threshold for each channel defined as the mean of the negative control intensities in each channel on the array provided a useful threshold for these customized microarrays. 31 Intensity values lower than the threshold in either channel were set equal to the threshold in that channel to avoid the computation of artificially large expression ratios. Each chip exhibited a clear, significant linear trend in Cy5 versus Cy3 measures, indicating a significant linear dye bias.…”

Section: Microarray Techniquementioning

confidence: 99%

“…For normalization purposes, 18S ribosomal RNA level was tested in parallel with the genes of interest. 31 Reactions were performed in a 96-well format in the BioRad iCycler iQ Real Time Detection System (BioRad Laboratories, Hercules, CA). For each gene, three independent PCR experiments from the same reverse transcription sample were performed.…”

Section: Real-time Polymerase Chain Reaction Assaysmentioning

confidence: 99%

See 2 more Smart Citations

A genomic and proteomic study of the spectrum of nonalcoholic fatty liver disease

et al. 2005

Self Cite

View full text Add to dashboard Cite

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and some of its forms are progressive. This study describes the profiling of hepatic gene expression and serum protein content in patients with different subtypes of NAFLD. Liver biopsy specimens from 98 bariatric surgery patients were classified as normal, steatosis alone, steatosis with nonspecific inflammation, and nonalcoholic steatohepatitis (NASH). Microarray hybridizations were performed in triplicate and the microarray expression levels of a selected group of genes were confirmed using real-time quantitative reverse-transcriptase polymerase chain reaction. Serum protein profiles of the same patients were determined by SELDI-TOF mass spectrometry. Of 98 obese patients, 91 were diagnosed with NAFLD (12 steatosis alone, 52 steatosis with nonspecific inflammation, and 27 NASH), and 7 patients without NAFLD served as obese controls. Each group of NAFLD patients was compared with the obese controls, and 22 genes with more than twofold differences in expression levels were revealed. Proteomics analyses were performed for the same group comparisons and revealed twelve significantly different protein peaks. In conclusion, this genomic/proteomic analysis suggests differential expression of several genes and protein peaks in patients within and across the forms of NAFLD. These findings may help clarify the pathogenesis of NAFLD and identify potential targets for therapeutic intervention. (HEPATOLOGY 2005;42:665-674.)

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Microarray Techniquementioning

confidence: 99%

Section: Real-time Polymerase Chain Reaction Assaysmentioning

confidence: 99%

See 1 more Smart Citation

A genomic and proteomic study of the spectrum of nonalcoholic fatty liver disease

et al. 2005

Self Cite

View full text Add to dashboard Cite

show abstract

“…A large number of studies have used microarrays to discern changes in gene expression patterns in well-defined cellular populations responding to a specific stimulus in vitro (23,24) or in complex clinical settings, such as cancer (25), where large changes in expression of individual genes have often been observed. Microarray technology has also been used to study NAFLD, and to date, there have been two high-throughput microarray studies of this disease (26,27). In the first, Sreekumar et al (26) examined gene expression levels in three distinct groups of cirrhotic patients: a group with cirrhosis secondary to NASH, a group with HCV-related cirrhosis, and a group with cirrhosis secondary to primary biliary cirrhosis (PBC).…”

Section: Microarray Technology To Gain Insight Into the Biochemical Pmentioning

confidence: 99%

“…The results highlighted the suppression of the genes involved in scavenging and reducing reactive oxygen species (ROS), this being especially prominent for superoxide dismutase 1 (SOD1); and other gene groups repressed in the NASH patients were those involved in fatty acid metabolism and glucose metabolism. In the second study, Younossi et al (27) examined the cDNA array of 5220 genes in three distinct groups: NASH patients, obese patients, and non-obese patients. The important findings were a decreased level of expression of fibrinogen-like 1 (FGL1), which is involved in liver regeneration; decreased expression of adrenomedullin, which protects the liver against organ damage via oxidative stress; and an increase in alfa-fetoprotein (AFP) production, all in the NASH patients.…”

Section: Microarray Technology To Gain Insight Into the Biochemical Pmentioning

confidence: 99%

Life Style-Related Diseases of the Digestive System: Gene Expression in Nonalcoholic Steatohepatitis Patients and Treatment Strategies

et al. 2007

View full text Add to dashboard Cite

Abstract. Nonalcoholic steatohepatitis (NASH) is a subset of nonalcoholic fatty liver disease (NAFLD) and sometimes progresses to cirrhosis and liver failure. We analyzed the expression profiles of approximately 50,000 genes and biological pathways in NASH patients in comparison with simple steatosis patients by using the analytical technique of GSEA (Gene Set Enrichment Analysis) by DNA microarrays. Although expressions of various genes were altered, GSEA showed clearly lower expression of nuclear receptors, including the peroxisome proliferatoractivated receptor gamma (PPARγ) pathway. In a preliminary study we therefore investigated the therapeutic effect of low-dose pioglitazone (15 mg / day per body for 24 weeks), a synthetic ligand for PPARγ, in 12 NASH patients. A decrease in aminotransferase (ALT) values to within the normal range was observed in 7 (58.3%) of the patients, and because the dose of pioglitazone was lower than that ordinarily used, no side effects, such as fatigue, lower extremity edema, or weight gain, were observed. In conclusion, the results confirmed involvement of the PPARγ pathway in NASH and the therapeutic utility of a PPARγ ligand.

show abstract

Genomics, Gene Arrays and Proteomics in the Study of Liver Disease

McCaughan¹,

Shackel²,

Williams³

et al. 2007

Textbook of Hepatology

View full text Add to dashboard Cite

Hepatic gene expression in patients with obesity‐related non‐alcoholic steatohepatitis

Cited by 106 publications

References 63 publications

A genomic and proteomic study of the spectrum of nonalcoholic fatty liver disease

A genomic and proteomic study of the spectrum of nonalcoholic fatty liver disease

Life Style-Related Diseases of the Digestive System: Gene Expression in Nonalcoholic Steatohepatitis Patients and Treatment Strategies

Genomics, Gene Arrays and Proteomics in the Study of Liver Disease

Contact Info

Product

Resources

About