Risk interaction of obesity, insulin resistance and hormone-sensitive lipase promoter polymorphisms (LIPE-60 C > G) in the development of fatty liver

BMC Med Genet. 2013 May 20:14:54. doi: 10.1186/1471-2350-14-54.

Abstract

Background: Hormone sensitive lipase (HSL) promoter (LIPE-60 C > G) polymorphism has been found to be involved in hepatic steatosis, obesity, diabetes and dyslipidemia. The precise interactions between these risk factors and genetic susceptibility that may affect non-alcoholic fatty liver disease (NAFLD) are still not fully determined.

Methods: A cross-sectional study was conducted in 1056 men. To avoid the confounding effect of plasma glucose, the study population was classified into normal glucose tolerance (NGT, n = 729) and glucose intolerance (GI, n = 299) groups. NAFLD was diagnosed by abdominal ultrasound after ruling out any history of alcohol abuse. A multivariate regression model was used to estimate the impact of these factors on NAFLD.

Results: In the NGT group, subjects with NAFLD often have complicated metabolic abnormalities. The coexistence of NAFLD and GI has been demonstrated to have a synergistic effect raising BMI, serum insulin and HOMA-insulin resistance (HOMA-IR). BMI and adipose-insulin resistance (Adipo-IR), but not HOMA-IR, significantly contributed to a greater risk of developing NAFLD. Serum triglyceride was significantly up-regulated in men with the (CG + GG) genotype of HSL promoter polymorphism, NAFLD and Adiopo-IR in sequence.

Conclusion: Adipo-IR, rather than HOMA-IR, appears to be a consistent insulin resistance index in the study of NAFLD. G allele of the HSL promoter polymorphism may contribute the greatest impact raising serum triglyceride in a state of glucose intolerance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cross-Sectional Studies
  • Ethanol / metabolism
  • Fatty Liver / enzymology
  • Fatty Liver / genetics*
  • Fatty Liver / metabolism*
  • Genetic Predisposition to Disease
  • Glucose Intolerance / genetics
  • Glucose Intolerance / metabolism
  • Humans
  • Insulin / blood
  • Insulin / genetics
  • Insulin / metabolism
  • Insulin Resistance / genetics*
  • Male
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease
  • Obesity / genetics*
  • Obesity / metabolism*
  • Polymorphism, Genetic
  • Promoter Regions, Genetic / genetics*
  • Risk Factors
  • Sterol Esterase / genetics*
  • Sterol Esterase / metabolism
  • Triglycerides / blood
  • Triglycerides / genetics
  • Triglycerides / metabolism

Substances

  • Insulin
  • Triglycerides
  • Ethanol
  • Sterol Esterase