Leptin receptor gene variation predicts weight change in subjects with impaired glucose tolerance

Obes Res. 2005 Mar;13(3):501-6. doi: 10.1038/oby.2005.52.


The leptin receptor (OB-R) gene is a promising candidate gene for type 2 diabetes, because leptin and its receptor play an important role in insulin secretion and the development of obesity. Therefore, we studied whether the pentanucleotide insertion polymorphism of the 3'-untranslated region (3'UTR) of the OB-R gene has an influence on the conversion from impaired glucose tolerance (IGT) to type 2 diabetes in the STOP-Noninsulin-Dependent Diabetes Mellitus trial. The STOP trial was a longitudinal, double-blind, placebo-controlled randomized trial that included 1429 subjects with IGT from high-risk populations. Using the restriction fragment length polymorphism method, we genotyped 770 subjects whose DNA was available for the insertion/deletion polymorphism of the 3'UTR of the OB-R gene. We did not find a relationship between the OB-R polymorphism and the conversion from IGT to type 2 diabetes (p = 0.747). However, the insertion allele was associated with a significant reduction in weight (p = 0.016), BMI (p = 0.009), and waist circumference (p = 0.006) in all subjects. Women carrying the I allele had a larger waist circumference change (p = 0.036), whereas men lost more weight and had a greater decrease in BMI. The pentanucleotide insertion/deletion polymorphism in the 3'UTR of the OB-R gene did not influence the conversion to type 2 diabetes in obese patients with IGT. However, this polymorphism was associated with a significant weight change, suggesting that it may potentially modulate the risk for type 2 diabetes.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Anthropometry
  • Body Mass Index
  • Body Weight*
  • DNA / analysis
  • Diabetes Mellitus, Type 2 / genetics
  • Double-Blind Method
  • Female
  • Genetic Variation / genetics*
  • Genotype
  • Glucose Intolerance / genetics*
  • Glucose Tolerance Test
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Obesity / genetics
  • Placebos
  • Polymorphism, Restriction Fragment Length
  • Receptors, Cell Surface / genetics*
  • Receptors, Leptin
  • Sex Characteristics
  • Weight Loss


  • LEPR protein, human
  • Placebos
  • Receptors, Cell Surface
  • Receptors, Leptin
  • DNA