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

J Clin Endocrinol Metab. 2005 Jul;90(7):4238-43. doi: 10.1210/jc.2004-2479. Epub 2005 Apr 26.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Cross-Sectional Studies
  • Female
  • Humans
  • Insulin Resistance*
  • Lipase / genetics*
  • Lipid Metabolism*
  • Liver / metabolism*
  • Male
  • PPAR gamma / genetics
  • Polymorphism, Genetic*

Substances

  • Cholesterol, HDL
  • Cholesterol, LDL
  • PPAR gamma
  • Lipase
  • hepatic lipase, human