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Association of leptin receptor polymorphism with insulin resistance.

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.