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

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.