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A case–control study on the effects of the apolipoprotein E genotypes in nonalcoholic fatty liver disease

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Abstract

Nonalcoholic fatty liver disease (NAFLD) has reached epidemic proportions being the most common cause of chronic liver disease in Western countries. The Apolipoprotein E (ApoE) gene has three major isoforms encoded by the ε2, ε3, and ε4 alleles, with the ε4 allele associated with hypercholesterolemia and the ε2 allele with the opposite effect. The role of apoE genotypes on NAFLD has been previously investigated with conflicting results. Our hospital-based case–control study conducted in Italy aims to explore the effect of the apoE genotypes on NAFLD risk and their effect on the clinical features of NAFLD patients. 310 NAFLD cases and 422 controls were genotyped for apoE. Adjusted odds ratios (ORs) and 95% confidence intervals (CI) from logistic regression were used to explore the relationship between NAFLD and apoE genotypes, as well as their interaction with selected demographic and lifestyle factors. ApoE ε4 allele carriers showed a statistically significant two-fold reduction of NAFLD risk (OR = 0.51, 95% CI: 0.28–0.93) compared with ε3 homozygotes. A statistically significant lower HDL cholesterol level was observed for ApoE ε4 carriers if compared with ε3/ε3 genotype or ApoE ε2 carriers with a nearly linear decreasing trend from ApoE ε2 to ApoE ε4 carriers. Our study reports for the first time a protective effect of the ε4 allele towards NAFLD that might be attributable to its role in the regulation of hepatic triglycerides rich very low-density lipoproteins secretion.

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Acknowledgments

We thank Benedetto Simone for his comments on the draft and the linguistic revision of the final manuscript.

Financial support: LM is supported byCofin Miur-Università Cattolica “Giovani Ricercatori 2002” and Istituto Toniolo Research Prize. AG is supported by Grant Miur-Università Cattolica Linea D.1. 2008. CC is supported by Young researcher 2009 Premio Livio Patrizi endorsed by SIMI (Soc. Italiana di Medicina Interna, Italian Society of Internal Medicine).

Conflict of interest

The authors declare they have no Conflict of interest.

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Authors and Affiliations

  1. Institute of Hygiene, Università Cattolica del Sacro Cuore, Rome, Italy

    Emma De Feo, Dario Arzani, Rosarita Amore, Walter Ricciardi & Stefania Boccia

  2. Department of Internal Medicine. Policlinico “A. Gemelli” Hospital, UCSC – Università Cattolica del Sacro Cuore, Largo A. Gemelli, 00168, Rome, Italy

    Consuelo Cefalo, Raffaele Landolfi, Antonio Grieco & Luca Miele

  3. IRCSS San Raffaele Pisana, Rome, Italy

    Stefania Boccia

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  1. Emma De Feo
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  2. Consuelo Cefalo
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  8. Luca Miele
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Correspondence to Luca Miele.

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De Feo, E., Cefalo, C., Arzani, D. et al. A case–control study on the effects of the apolipoprotein E genotypes in nonalcoholic fatty liver disease. Mol Biol Rep 39, 7381–7388 (2012). https://doi.org/10.1007/s11033-012-1570-7

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  • DOI: https://doi.org/10.1007/s11033-012-1570-7

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