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Hepatic Gene Expression of Caucasian and African-American Patients with Obesity-Related Non-Alcoholic Fatty Liver Disease

  • Clinical Research
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Abstract

Background/aim

There is increasing data suggesting that African Americans with NAFLD tend to have less progressive liver disease. The aim of this study is to assess differences in the hepatic gene expression of African-American and Caucasian patients with NAFLD who had undergone bariatric surgery.

Methods

A total of 94 patients (81 NAFLD and 13 weight-matched controls with normal liver biopsy) were included. Of the entire cohort, 73 were Caucasians and 21 were African Americans. All patients were undergoing bariatric surgery. Two liver biopsies were obtained at the time of surgery. One biopsy was snap-frozen for gene expression and the other biopsy was stained for pathologic assessment. Liver biopsy confirmed that 24 patients from our cohort had NASH while 57 had only simple steatosis. Snap-frozen liver biopsy specimens of these patients were then used for the RNA extraction. cDNA probes were hybridized with customized microarray gene chips containing 5,220 relevant genes. Gene expression profiles were compared between groups using significance analysis of microarrays algorithm.

Results

In comparison to all Caucasian patients, African-American patients had over-expression of EPB41L1, IGF2, FAH, ACSL4, FUT4, CYP3A (q values < 10−4). In comparison to Caucasian NAFLD patients, African-American NAFLD patients showed over-expression of EPB41L1 and ACSL4 genes. Finally, in comparison to Caucasian NASH patients, African-American NASH patients showed over-expression of GSTM 2, GSTM4 and GSTM5 as well as FH and ASCL4 genes. Some genes highlighted by this analysis, particularly cytochrome CYP3A and glutathione transferases GSTM2, 4, 5, were previously implicated in the pathogenesis of NASH.

Conclusion

African-American patients with biopsy-proven obesity-related NAFLD and NASH have a specific hepatic gene expression pattern that may explain their differences from Caucasian patients with NAFLD in developing progressive liver disease.

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Abbreviations

NAFLD:

Non-alcoholic fatty liver disease

NASH:

Non-alcoholic steatohepatitis

MS:

Metabolic syndrome

IR:

Insulin resistance

BMI:

Body mass index

SS:

Simple steatosis

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

HOMA:

Homeostasis model assessment

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Acknowledgment

This study was partly supported by the Liver Outcomes Research Fund of The Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, Virginia.

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Authors and Affiliations

  1. Center for Liver Diseases at Inova Fairfax Hospital, Falls Church, VA, USA

    Maria Stepanova, Arian Afendy, Ancha Baranova & Zobair Younossi

  2. Betty and Guy Beatty Center for Integrated Research, Inova Health System, 3300 Gallows Road, Falls Church, VA, 22042, USA

    Maria Stepanova, Noreen Hossain, Arian Afendy, Ancha Baranova & Zobair Younossi

  3. Molecular and Microbiology Department, College of Science, George Mason University, Falls Church, VA, USA

    Kellie Perry, Ancha Baranova & Zobair Younossi

  4. Armed Forces Institutes of Pathology, Washington, DC, USA

    Zachary D. Goodman

Authors
  1. Maria Stepanova
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  2. Noreen Hossain
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  3. Arian Afendy
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  4. Kellie Perry
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  5. Zachary D. Goodman
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  7. Zobair Younossi
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Correspondence to Zobair Younossi.

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Stepanova, M., Hossain, N., Afendy, A. et al. Hepatic Gene Expression of Caucasian and African-American Patients with Obesity-Related Non-Alcoholic Fatty Liver Disease. OBES SURG 20, 640–650 (2010). https://doi.org/10.1007/s11695-010-0078-2

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  • DOI: https://doi.org/10.1007/s11695-010-0078-2

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