Lack of an association between an apolipoprotein C3 genetic variant and the liver fat content in patients with type 2 diabetes

Authors

  • Jean Michel Petit M.D.,

    1. Institut National de la Santé et de la Recherche Médicale Unité 866 (Centre de Recherche), Centre Hospitalier Universitaire du Bocage Université de Bourgogne, Dijon, France
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  • Boris Guiu M.D.,

    1. Institut National de la Santé et de la Recherche Médicale Unité 866 (Centre de Recherche), Centre Hospitalier Universitaire du Bocage Université de Bourgogne, Dijon, France
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  • David Masson Ph.D.,

    1. Institut National de la Santé et de la Recherche Médicale Unité 866 (Centre de Recherche), Centre Hospitalier Universitaire du Bocage Université de Bourgogne, Dijon, France
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  • Jean-Pierre Cercueil M.D.,

    1. Institut National de la Santé et de la Recherche Médicale Unité 866 (Centre de Recherche), Centre Hospitalier Universitaire du Bocage Université de Bourgogne, Dijon, France
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  • Patrick Hillon M.D.,

    1. Institut National de la Santé et de la Recherche Médicale Unité 866 (Centre de Recherche), Centre Hospitalier Universitaire du Bocage Université de Bourgogne, Dijon, France
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  • Bruno Verges M.D.

    1. Institut National de la Santé et de la Recherche Médicale Unité 866 (Centre de Recherche), Centre Hospitalier Universitaire du Bocage Université de Bourgogne, Dijon, France
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  • Potential conflict of interest: Nothing to report.

To the Editor:

We read with great interest the article by Kozlitina et al.,1 who found no causal relationship between apolipoprotein C3 (APOC3) variants and hepatic triglyceride contents in middle-aged men and women. These results are not in accordance with a recent publication by Petersen et al.,2 who demonstrated that C-482T and T-455C polymorphisms in APOC3 are associated with nonalcoholic fatty liver disease (NAFLD) and insulin resistance. Even though NAFLD is well known to be associated with insulin resistance and diabetes mellitus, the link between certain genetic polymorphisms, NAFLD, and insulin resistance is quite complex. Indeed, the patatin-like phospholipase domain containing 3 (PNPLA3) polymorphism is strongly associated with NAFLD but not with obesity or insulin resistance.3, 4 In contrast, Petersen et al. found that genetic variants in APOC3 are associated with the liver fat content and insulin resistance; their results, however, have not been confirmed by Kozlitina et al. We recently published a study confirming that in people with type 2 diabetes, the liver fat content was related to the rs738409 PNPLA3 polymorphism.5 In this discordant context, we set out to determine whether the liver fat content, evaluated with proton magnetic resonance spectroscopy, was associated with the rs2854117 APOC3 polymorphism in this population. The study involved 253 patients with type 2 diabetes. One hundred fifty-eight patients (62.4%) had steatosis (hepatic triglyceride content >5.5%). In comparison with patients without steatosis, patients with steatosis had a higher body mass index, a higher visceral fat area, higher plasma alanine aminotransferase levels, higher plasma triglyceride levels, and lower plasma adiponectin levels.

The APOC3 rs2854117 variant was not associated with the liver fat content in our population (Table 1). No associations were found between this APOC3 variant and either the plasma triglyceride levels or the visceral fat area. In accordance with the study reported by Kozlitina et al.,1 our data for a specific population of patients with type 2 diabetes and a high prevalence of NAFLD suggest that the rs2854117 APOC3 genetic variant has little or no impact on the liver fat content.

Table 1. Clinical and Metabolic Characteristics of Patients With Type 2 Diabetes According to the APOC3 rs2854117 Polymorphism
CharacteristicWild-Type Homozygote (n = 124)Variant-Allele Carriers (n = 129)P Value
Age (years)62.1 ± 10.761.6 ± 9.50.79
Body mass index (kg/m2)34.5 ± 6.533.9 ± 6.90.90
Aspartate aminotransferase (IU/L)24.1 ± 18.122.9 ± 11.40.89
Alanine aminotransferase (IU/L)37.1 ± 21.640.1 ± 32.60.44
Plasma triglyceride level (mmol/L)2.25 ± 1.572.13 ± 1.530.24
Adiponectin plasma level (μg/mL)6.2 ± 4.75.9 ± 5.00.70
Visceral fat area (cm2)267 ± 109273 ± 890.42
Liver fat content (%)10.4 ± 8.510.7 ± 8.90.84
Steatosis: liver fat content > 5.5% [n (%)]76 (61.2)82 (63.5)0.79

Jean Michel Petit M.D.*, Boris Guiu M.D.*, David Masson M.D.*, Jean-Pierre Cercueil M.D.*, Patrick Hillon M.D.*, Bruno Verges M.D.*, * Institut National de la Santé et de la Recherche Médicale Unité 866 (Centre de Recherche), Centre Hospitalier Universitaire du Bocage, Université de Bourgogne, Dijon, France.

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