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.