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J Clin Endocrinol Metab. 2005 Jul;90(7):4238-43. Epub 2005 Apr 26.

Liver fat and insulin resistance are independently associated with the -514C>T polymorphism of the hepatic lipase gene.

Author information

1
Department of Internal Medicine, Division of Endocrinology, Metabolism, and Pathobiochemistry, University of Tübingen, Germany. norbert.stefan@med.uni-tuebingen.de

Abstract

CONTEXT:

Liver fat predicts insulin resistance in humans. So far, there is not much information on genetic determinants of liver fat. Hepatic lipase is a liver-specific enzyme that regulates lipid metabolism.

OBJECTIVE:

First, our object was to investigate whether the functional -514C>T polymorphism of the hepatic lipase gene is associated with liver fat content and with insulin sensitivity. Second, because this polymorphism displays gene-nutrient interactions, we assessed gene-gene interactions with the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma(2) on liver fat content and insulin sensitivity.

DESIGN AND METHODS:

Cross-sectional data from a total of 1070 nondiabetic subjects were analyzed. Insulin sensitivity was estimated from a 75-g oral glucose tolerance test. A subgroup of 115 subjects underwent measurements of liver fat.

RESULTS:

The -514C>T polymorphism of the hepatic lipase gene was associated with higher liver fat content (P = 0.005) and lower insulin sensitivity (P = 0.02), both after adjustment for age, gender, and percentage of body fat. This was independent of serum adiponectin concentrations (P = 0.01 and 0.03). However, there was an interaction of the -514C>T polymorphism with the Pro12Ala variant on liver fat (P = 0.09) and insulin sensitivity (P = 0.01). Subjects carrying the -514C>T polymorphism had higher liver fat content and were insulin resistant only before the background of the Pro/Pro genotype of the Pro12Ala polymorphism.

CONCLUSIONS:

The -514C>T polymorphism of the hepatic lipase gene is associated with higher liver fat content and lower whole-body insulin sensitivity. However, these effects are modulated by the common Pro12Ala polymorphism in peroxisome proliferator-activated receptor-gamma(2). These findings may be relevant for intervention strategies to prevent increase in liver fat content and insulin resistance.

PMID:
15855254
DOI:
10.1210/jc.2004-2479
[Indexed for MEDLINE]

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