We examined the genetic associations of the G-2548A polymorphism in the promoter of the leptin (LEP) gene and the Gln223Arg (Q223R) polymorphism of the leptin receptor (LEPR) gene with obesity. Two hundred twenty-six obese aboriginal subjects (BMI >= 27 kg/m(2)) and 182 aboriginal subjects with normal weight (BMI < 25 kg/m(2)) participated in this study. The polymorphisms of LEP G-2548A and LEPR Q223R were genotyped by polymerase chain reaction/restriction fragment length polymorphism, and their anthropometric characteristics were measured. Levels of leptin, triglycerides, and cholesterol were measured after overnight fasting. We found that the frequencies of the LEP G/G homozygote (22.6%) with Mendelian recessive (chi(2) = 7.89, p = 0.005) and codominant (chi(2) = 7.93, p = 0.02) models to be higher in the extremely obese subjects (BMI >=_ 35 kg/m(2)) than in normal weight subjects (6.9%) but not in moderately obese subjects (35 > BMI >= 27 kg/m(2)). There was no difference in genotypic frequency of the LEPR Q223R polymorphism between the extreme obese and control groups. We suggest that the LEP -2548 G/G homozygote plays a genetic recessive role in the development of extreme obesity in Taiwanese aborigines.
