Association of leptin receptor polymorphism with insulin resistance

Division of Clinical Epidemiology and Preventive Medicine, Department of Medicine, UCLA School of Medicine, University of California-Los Angeles, 924 Westwood Boulevard #335, Los Angeles, CA 90024, USA. kchiu@mednet.ucla.edu

OBJECTIVE: Although the role of the leptin receptor (LEPR) in obesity is well recognized, its role in insulin sensitivity remains unknown. DESIGN: This was a cross-sectional study to investigate the impact of the Q223R polymorphism of the LEPR gene on insulin sensitivity. METHODS: Sixty-seven glucose-tolerant Caucasians were enrolled. The insulin sensitivity index and glucose clearance were measured using a hyperglycemic clamp. Genomic DNA was extracted for genotyping. RESULTS: We identified 20 QQ, 31 QR, and 16 RR subjects. The three genotypic groups were similar in age, gender distribution, body mass index, waist-hip ratio, and blood pressure, but differed in the insulin sensitivity index (P=0.0180) and in glucose clearance (P=0.0220). Multivariate analyses showed that the Q223R polymorphism was independently associated with the insulin sensitivity index (P=0.0317) and glucose clearance (P=0.0436). A trend of increasing low density lipoprotein cholesterol concentration was also observed (P=0.0447). CONCLUSION: We have reported the first association of the Q223R polymorphism of the LEPR gene with insulin resistance.