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  • Open Access

Dissociation between APOC3 variants, hepatic triglyceride content and insulin resistance

Authors

  • Julia Kozlitina,

    1. McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX
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  • Eric Boerwinkle,

    1. Human Genetics Center and Institute for Molecular Medicine, University of Texas Health Science Center, Houston, TX
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  • Jonathan C. Cohen,

    Corresponding author
    1. McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX
    • McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390-8591
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    • fax: 214-647-7539

  • Helen H. Hobbs

    Corresponding author
    1. McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX
    2. Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX
    • McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390-8591
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  • Potential conflict of interest: Nothing to report.

Abstract

Nonalcoholic fatty liver disease (NAFLD) is an escalating health problem that is frequently associated with obesity and insulin resistance. The mechanistic relationship between NAFLD, obesity, and insulin resistance is not well understood. A nonsynonymous variant in patatin-like phospholipase domain containing 3 (rs738409, I148M) has been reproducibly associated with increased hepatic triglyceride content (HTGC) but has not been associated with either the body mass index (BMI) or indices of insulin resistance. Conversely, two sequence variants in apolipoprotein C3 (APOC3) that have been linked to hypertriglyceridemia (rs2854117 C > T and rs2854116 T > C) have recently been reported to be associated with both hepatic fat content and insulin resistance. Here we genotyped two APOC3 variants in 1228 African Americans, 843 European Americans and 426 Hispanics from a multiethnic population based study, the Dallas Heart Study and test for association with HTGC and homeostatic model of insulin resistance (HOMA-IR). We also examined the relationship between these two variants and HOMA-IR in the Atherosclerosis Risk in Communities (ARIC) study. No significant difference in hepatic fat content was found between carriers and noncarriers in the Dallas Heart Study. Neither APOC3 variant was associated with HOMA-IR in the Dallas Heart Study; this lack of association was confirmed in the ARIC study, even after the analysis was restricted to lean (BMI < 25 kg/m2) individuals (n = 4399). Conclusion: Our data do not support a causal relationship between these two variants in APOC3 and either HTGC or insulin resistance in middle-aged men and women. (HEPATOLOGY 2011;53:467-474)

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