Polymorphism of human leptin receptor gene is associated with type 2 diabetic patients complicated with non-alcoholic fatty liver disease in China

J Gastroenterol Hepatol. 2009 Feb;24(2):228-32. doi: 10.1111/j.1440-1746.2008.05544.x. Epub 2008 Aug 17.

Abstract

Background and aim: To investigate the relationship between human leptin receptor (LEPR) gene G3057A polymorphism and type 2 diabetes mellitus (T2DM) patients complicated with or without non-alcoholic fatty liver disease (NAFLD).

Methods: Two hundred and sixteen cases of newly diagnosed T2DM patients (104 cases complicated with NAFLD) and 108 cases of normal glucose tolerances (NGT) were recruited. Hemi-nested polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and PCR-direct sequence analysis were conducted to detect the polymorphism of LEPR G3057A variation. Plasma leptin levels were measured by enzyme-linked immunosorbent assay kit. Plasma lipid and glucose metabolic parameters were measured routinely. Liver ultrasound was carried out for all subjects.

Results: T2DM patients complicated with NAFLD had higher plasma insulin, leptin, triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) levels than those without NAFLD and NGT subjects. The variant frequency at nucleotide 3057 G-->A transversion was 76.0% in type 2 diabetic patients complicated with NAFLD, which was also significantly higher than those without NAFLD (62.1%) and NGT cases (53.2%). There was also significant difference in genotype distribution between the three groups (chi(2) = 14.63, P < 0.01).

Conclusion: The polymorphism of LEPR gene 3057 probably contributes to the onset of NAFLD by regulating lipid metabolism and affecting insulin sensitivity.

MeSH terms

  • Aged
  • Asian People / genetics*
  • Blood Glucose / analysis
  • Case-Control Studies
  • China / epidemiology
  • Cholesterol, LDL / blood
  • DNA Mutational Analysis
  • Diabetes Complications / blood
  • Diabetes Complications / ethnology
  • Diabetes Complications / genetics*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / ethnology
  • Diabetes Mellitus, Type 2 / genetics*
  • Fatty Liver / blood
  • Fatty Liver / ethnology
  • Fatty Liver / genetics*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Humans
  • Insulin / blood
  • Leptin / blood
  • Liver / chemistry
  • Liver / diagnostic imaging
  • Logistic Models
  • Male
  • Middle Aged
  • Phenotype
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Receptors, Leptin / genetics*
  • Risk Assessment
  • Risk Factors
  • Triglycerides / blood
  • Ultrasonography

Substances

  • Blood Glucose
  • Cholesterol, LDL
  • Insulin
  • LEPR protein, human
  • Leptin
  • Receptors, Leptin
  • Triglycerides