Leptin Receptor Gene Variation Predicts Weight Change in Subjects with Impaired Glucose Tolerance

Abstract 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.